bluuebunny/crossref_metadata_2025 huggingface dataset:
Data from Actinomycin D Targets NPM1c-Primed Mitochondria to Restore PML-Driven Senescence in AML Therapy
Authors: Wu Hsin-Chieh , Rérolle Domitille , Berthier Caroline , Hleihel Rita , Sakamoto Takashi , Quentin Samuel , Benhenda Shirine , Morganti Claudia , Wu Chengchen , Conte Lidio , Rimsky Sylvie , Sebert Marie , Clappier Emmanuelle , Souquere Sylvie , Gachet Stéphanie , Soulier Jean , Durand Sylvère , Trowbridge Jennifer J. , Bénit Paule , Rustin Pierre , El Hajj Hiba , Raffoux Emmanuel , Ades Lionel , Itzykson Raphael , Dombret Hervé , Fenaux Pierre , Espeli Olivier , Kroemer Guido , Brunetti Lorenzo , Mak Tak W. , Lallemand-Breitenbach Valérie , Bazarbachi Ali , Falini Brunangelo , Ito Keisuke , Martelli Maria Paola , de Thé Hugues
Published: April 2023

Abstract
Acute myeloid leukemia (AML) pathogenesis often involves a mutation in the NPM1 nucleolar chaperone, but the bases for its transforming properties and overall association with favorable therapeutic responses remain incompletely understood. Here we demonstrate that an oncogenic mutant form of NPM1 (NPM1c) impairs mitochondrial function. NPM1c also hampers formation of promyelocytic leukemia (PML) nuclear bodies (NB), which are regulators of mitochondrial fitness and key senescence effectors. Actinomycin D (ActD), an antibiotic with unambiguous clinical efficacy in relapsed/refractory NPM1c-AMLs, targets these primed mitochondria, releasing mitochondrial DNA, activating cyclic GMP-AMP synthase signaling, and boosting reactive oxygen species (ROS) production. The latter restore PML NB formation to drive TP53 activation and senescence of NPM1c-AML cells. In several models, dual targeting of mitochondria by venetoclax and ActD synergized to clear AML and prolong survival through targeting of PML. Our studies reveal an unexpected role for mitochondria downstream of NPM1c and implicate a mitochondrial/ROS/PML/TP53 senescence pathway as an effector of ActD-based therapies.
Significance:
ActD induces complete remissions in NPM1-mutant AMLs. We found that NPM1c affects mitochondrial biogenesis and PML NBs. ActD targets mitochondria, yielding ROS which enforce PML NB biogenesis and restore senescence. Dual targeting of mitochondria with ActD and venetoclax sharply potentiates their anti-AML activities in vivo.

This article is highlighted in the In This Issue feature, p. 2945
Data from EGFR Inhibition Potentiates FGFR Inhibitor Therapy and Overcomes Resistance in FGFR2 Fusion–Positive Cholangiocarcinoma
Authors: Wu Qibiao , Zhen Yuanli , Shi Lei , Vu Phuong , Greninger Patricia , Adil Ramzi , Merritt Joshua , Egan Regina , Wu Meng-Ju , Yin Xunqin , Ferrone Cristina R. , Deshpande Vikram , Baiev Islam , Pinto Christopher J. , McLoughlin Daniel E. , Walmsley Charlotte S. , Stone James R. , Gordan John D. , Zhu Andrew X. , Juric Dejan , Goyal Lipika , Benes Cyril H. , Bardeesy Nabeel
Published: April 2023

Abstract
FGFR inhibitors are approved for the treatment of advanced cholangiocarcinoma harboring FGFR2 fusions. However, the response rate is moderate, and resistance emerges rapidly due to acquired secondary FGFR2 mutations or due to other less-defined mechanisms. Here, we conducted high-throughput combination drug screens, biochemical analysis, and therapeutic studies using patient-derived models of FGFR2 fusion–positive cholangiocarcinoma to gain insight into these clinical profiles and uncover improved treatment strategies. We found that feedback activation of EGFR signaling limits FGFR inhibitor efficacy, restricting cell death induction in sensitive models and causing resistance in insensitive models lacking secondary FGFR2 mutations. Inhibition of wild-type EGFR potentiated responses to FGFR inhibitors in both contexts, durably suppressing MEK/ERK and mTOR signaling, increasing apoptosis, and causing marked tumor regressions in vivo. Our findings reveal EGFR-dependent adaptive signaling as an important mechanism limiting FGFR inhibitor efficacy and driving resistance and support clinical testing of FGFR/EGFR inhibitor therapy for FGFR2 fusion–positive cholangiocarcinoma.
Significance:
We demonstrate that feedback activation of EGFR signaling limits the effectiveness of FGFR inhibitor therapy and drives adaptive resistance in patient-derived models of FGFR2 fusion–positive cholangiocarcinoma. These studies support the potential of combination treatment with FGFR and EGFR inhibitors as an improved treatment for patients with FGFR2-driven cholangiocarcinoma.

This article is highlighted in the In This Issue feature, p. 1171
Data from Integrative RNA-omics Discovers GNAS Alternative Splicing as a Phenotypic Driver of Splicing Factor–Mutant Neoplasms
Authors: Wheeler Emily C. , Vora Shailee , Mayer Daniel , Kotini Andriana G. , Olszewska Malgorzata , Park Samuel S. , Guccione Ernesto , Teruya-Feldstein Julie , Silverman Lewis , Sunahara Roger K. , Yeo Gene W. , Papapetrou Eirini P.
Published: April 2023

Abstract
Mutations in splicing factors (SF) are the predominant class of mutations in myelodysplastic syndrome (MDS), but convergent downstream disease drivers remain elusive. To identify common direct targets of missplicing by mutant U2AF1 and SRSF2, we performed RNA sequencing and enhanced version of the cross-linking and immunoprecipitation assay in human hematopoietic stem/progenitor cells derived from isogenic induced pluripotent stem cell (iPSC) models. Integrative analyses of alternative splicing and differential binding converged on a long isoform of GNAS (GNAS-L), promoted by both mutant factors. MDS population genetics, functional and biochemical analyses support that GNAS-L is a driver of MDS and encodes a hyperactive long form of the stimulatory G protein alpha subunit, Gαs-L, that activates ERK/MAPK signaling. SF-mutant MDS cells have activated ERK signaling and consequently are sensitive to MEK inhibitors. Our findings highlight an unexpected and unifying mechanism by which SRSF2 and U2AF1 mutations drive oncogenesis with potential therapeutic implications for MDS and other SF-mutant neoplasms.
Significance:
SF mutations are disease-defining in MDS, but their critical effectors remain unknown. We discover the first direct target of convergent missplicing by mutant U2AF1 and SRSF2, a long GNAS isoform, which activates G protein and ERK/MAPK signaling, thereby driving MDS and rendering mutant cells sensitive to MEK inhibition.

This article is highlighted in the In This Issue feature, p. 587
Data from Precision Combination Therapies Based on Recurrent Oncogenic Coalterations
Authors: Li Xubin , Dowling Elisabeth K. , Yan Gonghong , Dereli Zeynep , Bozorgui Behnaz , Imanirad Parisa , Elnaggar Jacob H. , Luna Augustin , Menter David G. , Pilié Patrick G. , Yap Timothy A. , Kopetz Scott , Sander Chris , Korkut Anil
Published: April 2023

Abstract
Cancer cells depend on multiple driver alterations whose oncogenic effects can be suppressed by drug combinations. Here, we provide a comprehensive resource of precision combination therapies tailored to oncogenic coalterations that are recurrent across patient cohorts. To generate the resource, we developed Recurrent Features Leveraged for Combination Therapy (REFLECT), which integrates machine learning and cancer informatics algorithms. Using multiomic data, the method maps recurrent coalteration signatures in patient cohorts to combination therapies. We validated the REFLECT pipeline using data from patient-derived xenografts, in vitro drug screens, and a combination therapy clinical trial. These validations demonstrate that REFLECT-selected combination therapies have significantly improved efficacy, synergy, and survival outcomes. In patient cohorts with immunotherapy response markers, DNA repair aberrations, and HER2 activation, we have identified therapeutically actionable and recurrent coalteration signatures. REFLECT provides a resource and framework to design combination therapies tailored to tumor cohorts in data-driven clinical trials and preclinical studies.
Significance:
We developed the predictive bioinformatics platform REFLECT and a multiomics- based precision combination therapy resource. The REFLECT-selected therapies lead to significant improvements in efficacy and patient survival in preclinical and clinical settings. Use of REFLECT can optimize therapeutic benefit through selection of drug combinations tailored to molecular signatures of tumors.

See related commentary by Pugh and Haibe-Kains, p. 1416.

This article is highlighted in the In This Issue feature, p. 1397
Data from Dietary Lactobacillus-Derived Exopolysaccharide Enhances Immune-Checkpoint Blockade Therapy
Authors: Kawanabe-Matsuda Hirotaka , Takeda Kazuyoshi , Nakamura Marie , Makino Seiya , Karasaki Takahiro , Kakimi Kazuhiro , Nishimukai Megumi , Ohno Tatsukuni , Omi Jumpei , Kano Kuniyuki , Uwamizu Akiharu , Yagita Hideo , Boneca Ivo Gomperts , Eberl Gérard , Aoki Junken , Smyth Mark J. , Okumura Ko
Published: April 2023

Abstract
Microbes and their byproducts have been reported to regulate host health and immune functions. Here we demonstrated that microbial exopolysaccharide produced by Lactobacillus delbrueckii subsp. bulgaricus OLL1073R-1 (EPS-R1) induced CCR6+ CD8+ T cells of mice and humans. In mice, ingestion of EPS-R1 augmented antitumor effects of anti–CTLA-4 or anti–PD-1 monoclonal antibody against CCL20-expressing tumors, in which infiltrating CCR6+ CD8+ T cells were increased and produced IFNγ accompanied by a substantial immune response gene expression signature maintaining T-cell functions. Of note, the antitumor adjuvant effect of EPS-R1 was also observed in germ-free mice. Furthermore, the induction of CCR6 expression was mediated through the phosphorylated structure in EPS-R1 and a lysophosphatidic acid receptor on CD8+ T cells. Overall, we find that dietary EPS-R1 consumption induces CCR6+ CD8+ T cells in Peyer's patches, favoring a tumor microenvironment that augments the therapeutic effect of immune-checkpoint blockade depending on CCL20 production by tumors.
Significance:
Gut microbiota- and probiotic-derived metabolites are attractive agents to augment the efficacy of immunotherapies. Here we demonstrated that dietary consumption of Lactobacillus-derived exopolysaccharide induced CCR6+ CD8+ T cells in Peyer's patches and improved the tumor microenvironment to augment the therapeutic effects of immune-checkpoint blockade against CCL20-producing tumors.

See related commentary by Di Luccia and Colonna, p. 1189.

This article is highlighted in the In This Issue feature, p. 1171
Data from Human Bone Marrow Organoids for Disease Modeling, Discovery, and Validation of Therapeutic Targets in Hematologic Malignancies
Authors: Khan Abdullah O. , Rodriguez-Romera Antonio , Reyat Jasmeet S. , Olijnik Aude-Anais , Colombo Michela , Wang Guanlin , Wen Wei Xiong , Sousos Nikolaos , Murphy Lauren C. , Grygielska Beata , Perrella Gina , Mahony Christopher B. , Ling Rebecca E. , Elliott Natalina E. , Karali Christina Simoglou , Stone Andrew P. , Kemble Samuel , Cutler Emily A. , Fielding Adele K. , Croft Adam P. , Bassett David , Poologasundarampillai Gowsihan , Roy Anindita , Gooding Sarah , Rayes Julie , Machlus Kellie R. , Psaila Bethan
Published: April 2023

Abstract
A lack of models that recapitulate the complexity of human bone marrow has hampered mechanistic studies of normal and malignant hematopoiesis and the validation of novel therapies. Here, we describe a step-wise, directed-differentiation protocol in which organoids are generated from induced pluripotent stem cells committed to mesenchymal, endothelial, and hematopoietic lineages. These 3D structures capture key features of human bone marrow—stroma, lumen-forming sinusoids, and myeloid cells including proplatelet-forming megakaryocytes. The organoids supported the engraftment and survival of cells from patients with blood malignancies, including cancer types notoriously difficult to maintain ex vivo. Fibrosis of the organoid occurred following TGFβ stimulation and engraftment with myelofibrosis but not healthy donor–derived cells, validating this platform as a powerful tool for studies of malignant cells and their interactions within a human bone marrow–like milieu. This enabling technology is likely to accelerate the discovery and prioritization of novel targets for bone marrow disorders and blood cancers.
Significance:
We present a human bone marrow organoid that supports the growth of primary cells from patients with myeloid and lymphoid blood cancers. This model allows for mechanistic studies of blood cancers in the context of their microenvironment and provides a much-needed ex vivo tool for the prioritization of new therapeutics.

See related commentary by Derecka and Crispino, p. 263.

This article is highlighted in the In This Issue feature, p. 247
Data from C-CAT: The National Datacenter for Cancer Genomic Medicine in Japan
Authors: Kohno Takashi , Kato Mamoru , Kohsaka Shinji , Sudo Tomohisa , Tamai Ikuo , Shiraishi Yuichi , Okuma Yusuke , Ogasawara Daisuke , Suzuki Tatsuya , Yoshida Teruhiko , Mano Hiroyuki
Published: April 2023

Summary:
Since June 2019, under the umbrella of the national health insurance system, Japan has started cancer genomic medicine (CGM) with comprehensive genomic profiling (CGP) tests. The Ministry of Health, Labour and Welfare (MHLW) of Japan constructed a network of CGM hospitals (a total of 233 institutes as of July 1, 2022) and established the Center for Cancer Genomics and Advanced Therapeutics (C-CAT), the national datacenter for CGM. Clinical information and genomic data from the CGP tests are securely transferred to C-CAT, which then generates “C-CAT Findings” reports containing information of clinical annotation and matched clinical trials based on the CGP data. As of June 30, 2022, a total of 36,340 datapoints of clinical/genomic information are aggregated in C-CAT, and the number is expected to increase swiftly. The data are now open for sharing with not only the CGM hospitals but also other academic institutions and industries.
Data from Trastuzumab Deruxtecan in HER2-Positive Metastatic Breast Cancer Patients with Brain Metastases: A DESTINY-Breast01 Subgroup Analysis
Authors: Jerusalem Guy , Park Yeon Hee , Yamashita Toshinari , Hurvitz Sara A. , Modi Shanu , Andre Fabrice , Krop Ian E. , Gonzàlez Farré Xavier , You Benoit , Saura Cristina , Kim Sung-Bae , Osborne Cynthia R. , Murthy Rashmi K. , Gianni Lorenzo , Takano Toshimi , Liu Yali , Cathcart Jillian , Lee Caleb , Perrin Christophe
Published: April 2023

Abstract
DESTINY-Breast01 (NCT03248492) evaluated trastuzumab deruxtecan (T-DXd; DS-8201) in patients with heavily pretreated HER2-positive metastatic breast cancer (mBC). We present a subgroup of 24 patients with a history of treated brain metastases (BM), a population with limited treatment options. In patients with BMs, the confirmed objective response rate (cORR) was 58.3% [95% confidence interval (CI), 36.6%–77.9%], and the median progression-free survival (mPFS) was 18.1 months (95% CI, 6.7–18.1 months). In patients without BMs (n = 160), cORR was 61.3% and mPFS was 16.4 months. Eight patients (47.1%) experienced a best overall intracranial response of partial response or complete response. Seven patients (41.2%) had a best percentage change in brain lesion diameter from baseline consistent with stable disease. Two patients (8.3%) with BMs and two (1.3%) without BMs experienced progression in the brain. The safety profile of T-DXd was consistent with previous studies. The durable clinical activity of T-DXd in this population warrants further investigation.
Significance:
Advances in treating HER2-positive metastatic breast cancer have greatly improved patient outcomes, but intracranial progression remains an important risk for which few therapeutic options are currently available. T-DXd demonstrated durable efficacy in patients with stable, treated BMs.

This article is highlighted in the In This Issue feature, p. 2711
Data from Identifying the Transcriptional Drivers of Metastasis Embedded within Localized Melanoma
Authors: Suresh Shruthy , Rabbie Roy , Garg Manik , Lumaquin Dianne , Huang Ting-Hsiang , Montal Emily , Ma Yilun , Cruz Nelly M , Tang Xinran , Nsengimana Jérémie , Newton-Bishop Julia , Hunter Miranda V. , Zhu Yuxin , Chen Kevin , de Stanchina Elisa , Adams David J. , White Richard M.
Published: April 2023

Abstract
In melanoma, predicting which tumors will ultimately metastasize guides treatment decisions. Transcriptional signatures of primary tumors have been utilized to predict metastasis, but which among these are driver or passenger events remains unclear. We used data from the adjuvant AVAST-M trial to identify a predictive gene signature in localized tumors that ultimately metastasized. Using a zebrafish model of primary melanoma, we interrogated the top genes from the AVAST-M signature in vivo. This identified GRAMD1B, a cholesterol transfer protein, as a bona fide metastasis suppressor, with a majority of knockout animals rapidly developing metastasis. Mechanistically, excess free cholesterol or its metabolite 27-hydroxycholesterol promotes invasiveness via activation of an AP-1 program, which is associated with increased metastasis in humans. Our data demonstrate that the transcriptional seeds of metastasis are embedded within localized tumors, suggesting that early targeting of these programs can be used to prevent metastatic relapse.
Significance:
We analyzed human melanoma transcriptomics data to identify a gene signature predictive of metastasis. To rapidly test clinical signatures, we built a genetic metastasis platform in adult zebrafish and identified GRAMD1B as a suppressor of melanoma metastasis. GRAMD1B-associated cholesterol overload activates an AP-1 program to promote melanoma invasion.

This article is highlighted in the In This Issue feature, p. 1
Data from BAF Complex Maintains Glioma Stem Cells in Pediatric H3K27M Glioma
Authors: Panditharatna Eshini , Marques Joana G. , Wang Tingjian , Trissal Maria C. , Liu Ilon , Jiang Li , Beck Alexander , Groves Andrew , Dharia Neekesh V. , Li Deyao , Hoffman Samantha E. , Kugener Guillaume , Shaw McKenzie L. , Mire Hafsa M. , Hack Olivia A. , Dempster Joshua M. , Lareau Caleb , Dai Lingling , Sigua Logan H. , Quezada Michael A. , Stanton Ann-Catherine J. , Wyatt Meghan , Kalani Zohra , Goodale Amy , Vazquez Francisca , Piccioni Federica , Doench John G. , Root David E. , Anastas Jamie N. , Jones Kristen L. , Conway Amy Saur , Stopka Sylwia , Regan Michael S. , Liang Yu , Seo Hyuk-Soo , Song Kijun , Bashyal Puspalata , Jerome William P. , Mathewson Nathan D. , Dhe-Paganon Sirano , Suvà Mario L. , Carcaboso Angel M. , Lavarino Cinzia , Mora Jaume , Nguyen Quang-De , Ligon Keith L. , Shi Yang , Agnihotri Sameer , Agar Nathalie Y.R. , Stegmaier Kimberly , Stiles Charles D. , Monje Michelle , Golub Todd R. , Qi Jun , Filbin Mariella G.
Published: April 2023

Abstract
Diffuse midline gliomas are uniformly fatal pediatric central nervous system cancers that are refractory to standard-of-care therapeutic modalities. The primary genetic drivers are a set of recurrent amino acid substitutions in genes encoding histone H3 (H3K27M), which are currently undruggable. These H3K27M oncohistones perturb normal chromatin architecture, resulting in an aberrant epigenetic landscape. To interrogate for epigenetic dependencies, we performed a CRISPR screen and show that patient-derived H3K27M-glioma neurospheres are dependent on core components of the mammalian BAF (SWI/SNF) chromatin remodeling complex. The BAF complex maintains glioma stem cells in a cycling, oligodendrocyte precursor cell–like state, in which genetic perturbation of the BAF catalytic subunit SMARCA4 (BRG1), as well as pharmacologic suppression, opposes proliferation, promotes progression of differentiation along the astrocytic lineage, and improves overall survival of patient-derived xenograft models. In summary, we demonstrate that therapeutic inhibition of the BAF complex has translational potential for children with H3K27M gliomas.
Significance:
Epigenetic dysregulation is at the core of H3K27M-glioma tumorigenesis. Here, we identify the BRG1–BAF complex as a critical regulator of enhancer and transcription factor landscapes, which maintain H3K27M glioma in their progenitor state, precluding glial differentiation, and establish pharmacologic targeting of the BAF complex as a novel treatment strategy for pediatric H3K27M glioma.

See related commentary by Beytagh and Weiss, p. 2730.

See related article by Mo et al., p. 2906.

This article is highlighted in the In This Issue feature, p. 2711
Data from Proteogenomic Markers of Chemotherapy Resistance and Response in Triple-Negative Breast Cancer
Authors: Anurag Meenakshi , Jaehnig Eric J. , Krug Karsten , Lei Jonathan T. , Bergstrom Erik J. , Kim Beom-Jun , Vashist Tanmayi D. , Huynh Anh Minh Tran , Dou Yongchao , Gou Xuxu , Huang Chen , Shi Zhiao , Wen Bo , Korchina Viktoriya , Gibbs Richard A. , Muzny Donna M. , Doddapaneni Harshavardhan , Dobrolecki Lacey E. , Rodriguez Henry , Robles Ana I. , Hiltke Tara , Lewis Michael T. , Nangia Julie R. , Nemati Shafaee Maryam , Li Shunqiang , Hagemann Ian S. , Hoog Jeremy , Lim Bora , Osborne C. Kent , Mani D.R. , Gillette Michael A. , Zhang Bing , Echeverria Gloria V. , Miles George , Rimawi Mothaffar F. , Carr Steven A. , Ademuyiwa Foluso O. , Satpathy Shankha , Ellis Matthew J.
Published: April 2023

Abstract
Microscaled proteogenomics was deployed to probe the molecular basis for differential response to neoadjuvant carboplatin and docetaxel combination chemotherapy for triple-negative breast cancer (TNBC). Proteomic analyses of pretreatment patient biopsies uniquely revealed metabolic pathways, including oxidative phosphorylation, adipogenesis, and fatty acid metabolism, that were associated with resistance. Both proteomics and transcriptomics revealed that sensitivity was marked by elevation of DNA repair, E2F targets, G2–M checkpoint, interferon-gamma signaling, and immune-checkpoint components. Proteogenomic analyses of somatic copy-number aberrations identified a resistance-associated 19q13.31–33 deletion where LIG1, POLD1, and XRCC1 are located. In orthogonal datasets, LIG1 (DNA ligase I) gene deletion and/or low mRNA expression levels were associated with lack of pathologic complete response, higher chromosomal instability index (CIN), and poor prognosis in TNBC, as well as carboplatin-selective resistance in TNBC preclinical models. Hemizygous loss of LIG1 was also associated with higher CIN and poor prognosis in other cancer types, demonstrating broader clinical implications.
Significance:
Proteogenomic analysis of triple-negative breast tumors revealed a complex landscape of chemotherapy response associations, including a 19q13.31–33 somatic deletion encoding genes serving lagging-strand DNA synthesis (LIG1, POLD1, and XRCC1), that correlate with lack of pathologic response, carboplatin-selective resistance, and, in pan-cancer studies, poor prognosis and CIN.

This article is highlighted in the In This Issue feature, p. 2483
Data from Serial Profiling of Circulating Tumor DNA Identifies Dynamic Evolution of Clinically Actionable Genomic Alterations in High-Risk Neuroblastoma
Authors: Bosse Kristopher R. , Giudice Anna Maria , Lane Maria V. , McIntyre Brendan , Schürch Patrick M. , Pascual-Pasto Guillem , Buongervino Samantha N. , Suresh Sriyaa , Fitzsimmons Alana , Hyman Adam , Gemino-Borromeo Maria , Saggio Jennifer , Berko Esther R. , Daniels Alexander A. , Stundon Jennifer , Friedrichsen Megan , Liu Xin , Margolis Matthew L. , Li Marilyn M. , Tierno Marni Brisson , Oxnard Geoffrey R. , Maris John M. , Mossé Yael P.
Published: April 2023

Abstract
Neuroblastoma evolution, heterogeneity, and resistance remain inadequately defined, suggesting a role for circulating tumor DNA (ctDNA) sequencing. To define the utility of ctDNA profiling in neuroblastoma, 167 blood samples from 48 high-risk patients were evaluated for ctDNA using comprehensive genomic profiling. At least one pathogenic genomic alteration was identified in 56% of samples and 73% of evaluable patients, including clinically actionable ALK and RAS–MAPK pathway variants. Fifteen patients received ALK inhibition (ALKi), and ctDNA data revealed dynamic genomic evolution under ALKi therapeutic pressure. Serial ctDNA profiling detected disease evolution in 15 of 16 patients with a recurrently identified variant—in some cases confirming disease progression prior to standard surveillance methods. Finally, ctDNA-defined ERRFI1 loss-of-function variants were validated in neuroblastoma cellular models, with the mutant proteins exhibiting loss of wild-type ERRFI1's tumor-suppressive functions. Taken together, ctDNA is prevalent in children with high-risk neuroblastoma and should be followed throughout neuroblastoma treatment.
Significance:
ctDNA is prevalent in children with neuroblastoma. Serial ctDNA profiling in patients with neuroblastoma improves the detection of potentially clinically actionable and functionally relevant variants in cancer driver genes and delineates dynamic tumor evolution and disease progression beyond that of standard tumor sequencing and clinical surveillance practices.

See related commentary by Deubzer et al., p. 2727.

This article is highlighted in the In This Issue feature, p. 2711
Data from Human Papillomavirus 42 Drives Digital Papillary Adenocarcinoma and Elicits a Germ Cell–like Program Conserved in HPV-Positive Cancers
Authors: Leiendecker Lukas , Neumann Tobias , Jung Pauline S. , Cronin Shona M. , Steinacker Thomas L. , Schleiffer Alexander , Schutzbier Michael , Mechtler Karl , Kervarrec Thibault , Laurent Estelle , Bachiri Kamel , Coyaud Etienne , Murali Rajmohan , Busam Klaus J. , Itzinger-Monshi Babak , Kirnbauer Reinhard , Cerroni Lorenzo , Calonje Eduardo , Rütten Arno , Stubenrauch Frank , Griewank Klaus G. , Wiesner Thomas , Obenauf Anna C.
Published: April 2023

Abstract
The skin is exposed to viral pathogens, but whether they contribute to the oncogenesis of skin cancers has not been systematically explored. Here we investigated 19 skin tumor types by analyzing off-target reads from commonly available next-generation sequencing data for viral pathogens. We identified human papillomavirus 42 (HPV42) in 96% (n = 45/47) of digital papillary adenocarcinoma (DPA), an aggressive cancer occurring on the fingers and toes. We show that HPV42, so far considered a nononcogenic, “low-risk” HPV, recapitulates the molecular hallmarks of oncogenic, “high-risk” HPVs. Using machine learning, we find that HPV-driven transformation elicits a germ cell–like transcriptional program conserved throughout all HPV-driven cancers (DPA, cervical carcinoma, and head and neck cancer). We further show that this germ cell–like transcriptional program, even when reduced to the top two genes (CDKN2A and SYCP2), serves as a fingerprint of oncogenic HPVs with implications for early detection, diagnosis, and therapy of all HPV-driven cancers.
Significance:
We identify HPV42 as a uniform driver of DPA and add a new member to the short list of tumorigenic viruses in humans. We discover that all oncogenic HPVs evoke a germ cell–like transcriptional program with important implications for detecting, diagnosing, and treating all HPV-driven cancers.

See related commentary by Starrett et al., p. 17.

This article is highlighted in the In This Issue feature, p. 1
Supplementary Table S4 from Phase II Study of Personalized Peptide Vaccination for Previously Treated Advanced Colorectal Cancer
Authors: Kibe Shiro , Yutani Shigeru , Motoyama Satoru , Nomura Takanobu , Tanaka Natsuki , Kawahara Akihiko , Yamaguchi Tomohiko , Matsueda Satoko , Komatsu Nobukazu , Miura Masatomo , Hinai Yudai , Hattori Satoshi , Yamada Akira , Kage Masayoshi , Itoh Kyogo , Akagi Yoshito , Sasada Tetsuro
Published: April 2023

Immune responses to the administered peptides.
Supplementary Methods from Phase II Study of Personalized Peptide Vaccination for Previously Treated Advanced Colorectal Cancer
Authors: Kibe Shiro , Yutani Shigeru , Motoyama Satoru , Nomura Takanobu , Tanaka Natsuki , Kawahara Akihiko , Yamaguchi Tomohiko , Matsueda Satoko , Komatsu Nobukazu , Miura Masatomo , Hinai Yudai , Hattori Satoshi , Yamada Akira , Kage Masayoshi , Itoh Kyogo , Akagi Yoshito , Sasada Tetsuro
Published: April 2023

Supplementary Methods
Supplementary Figure S1 from Phase II Study of Personalized Peptide Vaccination for Previously Treated Advanced Colorectal Cancer
Authors: Kibe Shiro , Yutani Shigeru , Motoyama Satoru , Nomura Takanobu , Tanaka Natsuki , Kawahara Akihiko , Yamaguchi Tomohiko , Matsueda Satoko , Komatsu Nobukazu , Miura Masatomo , Hinai Yudai , Hattori Satoshi , Yamada Akira , Kage Masayoshi , Itoh Kyogo , Akagi Yoshito , Sasada Tetsuro
Published: April 2023

Immunohistochemical analysis of vaccine antigen expressions in CRC tissues.
Suppl Movie 9 from Cytotoxic T Lymphocyte Antigen-4 Blockade Enhances Antitumor Immunity by Stimulating Melanoma-Specific T-cell Motility
Authors: Pentcheva-Hoang Tsvetelina , Simpson Tyler R. , Montalvo-Ortiz Welby , Allison James P.
Published: April 2023

Pmel-1 dynamics in TDLN prior to injection of α-CD28 antibodies.
Suppl Movie 11 from Cytotoxic T Lymphocyte Antigen-4 Blockade Enhances Antitumor Immunity by Stimulating Melanoma-Specific T-cell Motility
Authors: Pentcheva-Hoang Tsvetelina , Simpson Tyler R. , Montalvo-Ortiz Welby , Allison James P.
Published: April 2023

Pmel-1 dynamics in TDLN prior to injection of hamster Ig.
Suppl Movie 10 from Cytotoxic T Lymphocyte Antigen-4 Blockade Enhances Antitumor Immunity by Stimulating Melanoma-Specific T-cell Motility
Authors: Pentcheva-Hoang Tsvetelina , Simpson Tyler R. , Montalvo-Ortiz Welby , Allison James P.
Published: April 2023

Pmel-1 dynamics in TDLN subsequent to injection of α-CD28 antibodies.
Supplementary Figure 2 from Epigenetic Potentiation of NY-ESO-1 Vaccine Therapy in Human Ovarian Cancer
Authors: Odunsi Kunle , Matsuzaki Junko , James Smitha R. , Mhawech-Fauceglia Paulette , Tsuji Takemasa , Miller Austin , Zhang Wa , Akers Stacey N. , Griffiths Elizabeth A. , Miliotto Anthony , Beck Amy , Batt Carl A. , Ritter Gerd , Lele Shashikant , Gnjatic Sacha , Karpf Adam R.
Published: April 2023

PDF file - 54K, Figure S2. Recognition of naturally processed NY-ESO-1 antigen by NY-ESO-1 specific T cells, pre- and post-therapy.
Supplementary Figure 1 from Epigenetic Potentiation of NY-ESO-1 Vaccine Therapy in Human Ovarian Cancer
Authors: Odunsi Kunle , Matsuzaki Junko , James Smitha R. , Mhawech-Fauceglia Paulette , Tsuji Takemasa , Miller Austin , Zhang Wa , Akers Stacey N. , Griffiths Elizabeth A. , Miliotto Anthony , Beck Amy , Batt Carl A. , Ritter Gerd , Lele Shashikant , Gnjatic Sacha , Karpf Adam R.
Published: April 2023

PDF file - 51K, Figure S1. NY-ESO-1-specific CD8+ T cell response to a melanoma cell line.
Supplementary Figure 3 from Combining Oncolytic HSV-1 with Immunogenic Cell Death-Inducing Drug Mitoxantrone Breaks Cancer Immune Tolerance and Improves Therapeutic Efficacy
Authors: Workenhe Samuel T. , Pol Jonathan G. , Lichty Brian D. , Cummings Derek T. , Mossman Karen L.
Published: April 2023

PDF file - 332K, Supplementary figure 3. Antigen presenting cells infiltrating treated tumors
Supplementary Figure 1 from Combining Oncolytic HSV-1 with Immunogenic Cell Death-Inducing Drug Mitoxantrone Breaks Cancer Immune Tolerance and Improves Therapeutic Efficacy
Authors: Workenhe Samuel T. , Pol Jonathan G. , Lichty Brian D. , Cummings Derek T. , Mossman Karen L.
Published: April 2023

PDF file - 205K, Supplementary figure 1. Addition of MTX does not enhance KM100 virus replication
Supplementary Methods from JAK2 Expression Is Associated with Tumor-Infiltrating Lymphocytes and Improved Breast Cancer Outcomes: Implications for Evaluating JAK2 Inhibitors
Authors: Miller Chris P. , Thorpe Jason D. , Kortum Amanda N. , Coy Catherine M. , Cheng Wei-Yi , Yang Tai-Hsien Ou , Anastassiou Dimitris , Beatty J. David , Urban Nicole D. , Blau C. Anthony
Published: April 2023

PDF file - 33K
Supplementary Table 1 from Chemoimmunotherapy Using Pegylated Liposomal Doxorubicin and Interleukin-18 in Recurrent Ovarian Cancer: A Phase I Dose-Escalation Study
Authors: Simpkins Fiona , Flores Aurea , Chu Christina , Berek Jonathan S. , Lucci Joseph , Murray Sharon , Bauman John , Struemper Herbert , Germaschewski Fiona , Jonak Zdenka , Gardner Olivia , Toso John , Coukos George
Published: April 2023

PDF file - 46K, Patient Demographics and Disease Characteristics.
Supplementary Table 1, Figures 1 - 3 from A Transient Increase in Eosinophils Is Associated with Prolonged Survival in Men with Metastatic Castration-Resistant Prostate Cancer Who Receive Sipuleucel-T
Authors: McNeel Douglas G. , Gardner Thomas A. , Higano Celestia S. , Kantoff Philip W. , Small Eric J. , Wener Mark H. , Sims Robert B. , DeVries Todd , Sheikh Nadeem A. , Dreicer Robert
Published: April 2023

Supplementary Table S1. Baseline demographics and disease characteristics in patients with mCRPC from the phase III sipuleucel-T trials included in the eosinophil analysis and the overall pooled population. Supplementary Figure S1. Overview of the study designs of three phase III clinical trials from which data were pooled for this retrospective analysis. Supplementary Figure S2. Changes in eosinophil counts for sipuleucel-T-treated patients with or without an elevated eosinophil count in randomized phase III trials, versus the control group. Supplementary Figure S3. Association of immune response with change in eosinophil counts for sipuleucel-T-treated patients in randomized phase III trials.
Supplementary Figures 1-5 and Supplementary Tables 1-3 from T-cell Localization, Activation, and Clonal Expansion in Human Pancreatic Ductal Adenocarcinoma
Authors: Stromnes Ingunn M. , Hulbert Ayaka , Pierce Robert H. , Greenberg Philip D. , Hingorani Sunil R.
Published: April 2023

S1. TLS composition and immunological features of resected PDA. S2. Gating strategy for analyzing CD244 (2B4) and Tim3 expression on CD8 T cells in blood of normal individuals (Nl), in blood of PDA patients (PDA blood) and in tumors. S3. Representative human PDA section stained with the multiplex immunohistochemical panel. S4. Representative images of human PDA from the multiplex without (top row, A and B) and with (bottom, C and D), the stromal vs. tumor regions demarcated and cell numbers quantified. S5. PD-L1+ stromal cells in PDA include CD163+ macrophages (Figure 6A) as well as an additional CD163- cell subset shown here. Supplementary Table 1. Antibodies used for tissue multiplex in Figure 6. Supplementary Table 2. Patient characteristics. Supplementary Table 3. TCRβ CDR3 sequence data in blood and tumors from PDA patients.
Supplemental figures 1-4 and supplemental figure legends from Immunosurveillance and Immunoediting of Breast Cancer via Class I MHC Receptors
Authors: Tu Megan M. , Rahim Mir Munir A. , Sayed Céline , Mahmoud Ahmad Bakur , Makrigiannis Andrew P.
Published: April 2023

Supp 1. Analysis of tumor-infiltrating lymphocytes in E0771-induced mammary tumors. Supp 2. Splenocytes from tumor-bearing MMTV-PyVTTg mice are not activated. Supp 3. Analysis of tumor-infiltrating lymphocytes in mammary tumors from MMTV-14 PyVTTg mice. Supp 4. FasL and TRAIL are not expressed on tumor-infiltrating NK cells in MMTV-22 PyVTTg mice.
Figure S2 from Programmed Cell Death Ligand 1 (PD-L1) Signaling Regulates Macrophage Proliferation and Activation
Authors: Hartley Genevieve P. , Chow Lyndah , Ammons Dylan T. , Wheat William H. , Dow Steven W.
Published: April 2023

Supplemental Figure S2. PD-L1 antibody treatment of human macrophages results in phenotypic changes consistent with those seen in murine macrophages. Macrophages were treated with medium only, an irrelevant isotype antibody, or PD-L1 antibody for 6 days, and images were taken of the cells to assess changes in morphology. A non-commercial antibody (A) and Tecentriq (B) were both tested, and changes in confluence (C) were measured every 3 hours for the 6 days with an IncuCyte ZOOM live cell imaging system. An MTT was performed to measure survival of the cells and mean absorbances of MTT substrate were compared statistically with one-way ANOVA and Prism7 software (D). Lastly, surface expression of co-stimulatory molecules (CD40 and CD86) by macrophages treated with the non-commercial antibody (D) and with Tecentriq (F) was compared to control macrophages by flow cytometry using two-way ANOVA and Prism7 software. Statistically significant differences were denoted as P-value * < 0.05, ** < 0.005, *** < 0.0005 and **** < 0.0001, with similar results obtained in 2 independent experiments.
Supplementary Table 2 from Assessment of MAGE-A Expression in Resected Non–Small Cell Lung Cancer in Relation to Clinicopathologic Features and Mutational Status of EGFR and KRAS
Authors: Ayyoub Maha , Memeo Lorenzo , Álvarez-Fernández Emilio , Colarossi Cristina , Costanzo Rosario , Aiello Eleonora , Martinetti Daniela , Valmori Danila
Published: April 2023

PDF file - 78K, Type of KRAS and EGFR mutations in NSCLC tumors of different histological subtypes.
Supplementary Figure 1 from Assessment of MAGE-A Expression in Resected Non–Small Cell Lung Cancer in Relation to Clinicopathologic Features and Mutational Status of EGFR and KRAS
Authors: Ayyoub Maha , Memeo Lorenzo , Álvarez-Fernández Emilio , Colarossi Cristina , Costanzo Rosario , Aiello Eleonora , Martinetti Daniela , Valmori Danila
Published: April 2023

PDF file - 570K, Correlation between tumors histological type and grade and disease stage and patients' survival. Analysis of disease-specific survival of patients was assessed using Kaplan-Meier curves and statistical significance of the difference between the groups was determined using the Log-Rank test.
Figure S7 from Human GUCY2C-Targeted Chimeric Antigen Receptor (CAR)-Expressing T Cells Eliminate Colorectal Cancer Metastases
Authors: Magee Michael S. , Abraham Tara S. , Baybutt Trevor R. , Flickinger John C. , Ridge Natalie A. , Marszalowicz Glen P. , Prajapati Priyanka , Hersperger Adam R. , Waldman Scott A. , Snook Adam E.
Published: April 2023

Figure S7 shows cytokine production by 5F9.m28BBz CAR-T cells stimulated by CT26.hGUCY2C cells.
Figure S1 from Human GUCY2C-Targeted Chimeric Antigen Receptor (CAR)-Expressing T Cells Eliminate Colorectal Cancer Metastases
Authors: Magee Michael S. , Abraham Tara S. , Baybutt Trevor R. , Flickinger John C. , Ridge Natalie A. , Marszalowicz Glen P. , Prajapati Priyanka , Hersperger Adam R. , Waldman Scott A. , Snook Adam E.
Published: April 2023

Figure S1 shows the codon-optimized sequence of human GUCY2C.
Supplementary Methods from Role of Crosslinking for Agonistic CD40 Monoclonal Antibodies as Immune Therapy of Cancer
Authors: Richman Lee P. , Vonderheide Robert H.
Published: April 2023

PDF file - 62K
Supplemental Table 1 from PD-L1 microSPECT/CT Imaging for Longitudinal Monitoring of PD-L1 Expression in Syngeneic and Humanized Mouse Models for Cancer
Authors: Heskamp Sandra , Wierstra Peter J. , Molkenboer-Kuenen Janneke D.M. , Sandker Gerwin W. , Thordardottir Soley , Cany Jeannette , Olive Daniel , Bussink Johan , Boerman Otto C. , Dolstra Harry , Aarntzen Erik H.J.G. , Hobo Willemijn A.
Published: April 2023

Supplemental Table 1
Supplementary Figure 2 from Splenectomy Promotes Indirect Elimination of Intraocular Tumors by CD8+ T Cells That Is Associated with IFNγ- and Fas/FasL-Dependent Activation of Intratumoral Macrophages
Authors: Miller Maxine R. , Mandell Jonathan B. , Beatty Kelly M. , Harvey Stephen A.K. , Rizzo Michael J. , Previte Dana M. , Thorne Stephen H. , McKenna Kyle C.
Published: April 2023

IFNγ resistance in E.G7-OVA and P815 tumors.
Supplementary Figure 3 from Immune Consequences of Decreasing Tumor Vasculature with Antiangiogenic Tyrosine Kinase Inhibitors in Combination with Therapeutic Vaccines
Authors: Farsaci Benedetto , Donahue Renee N. , Coplin Michael A. , Grenga Italia , Lepone Lauren M. , Molinolo Alfredo A. , Hodge James W.
Published: April 2023

Effect of sunitinib or sorafenib in combination with rMVATwist- TRICOM vaccine on tumor compactness in the 4T1 breast cancer model.
Data Supplement from Immune Consequences of Decreasing Tumor Vasculature with Antiangiogenic Tyrosine Kinase Inhibitors in Combination with Therapeutic Vaccines
Authors: Farsaci Benedetto , Donahue Renee N. , Coplin Michael A. , Grenga Italia , Lepone Lauren M. , Molinolo Alfredo A. , Hodge James W.
Published: April 2023

Supplementary Materials and Methods; Figure Legends
Supplementary Figures 1 - 6 from Paradoxical Activation of T Cells via Augmented ERK Signaling Mediated by a RAF Inhibitor
Authors: Callahan Margaret K. , Masters Gregg , Pratilas Christine A. , Ariyan Charlotte , Katz Jessica , Kitano Shigehisa , Russell Valerie , Gordon Ruth Ann , Vyas Shachi , Yuan Jianda , Gupta Ashok , Wigginton Jon M. , Rosen Neal , Merghoub Taha , Jure-Kunkel Maria , Wolchok Jedd D.
Published: April 2023

PDF file - 528K, Supplementary Figure 1. BMS908662 enhances human T cell activation in vitro in a concentration-dependent manner. Supplementary Figure 2. BMS908662 inhibits the growth of BRAF mutant tumor cells in vitro. Supplementary Figure 3. BMS908662 enhances murine T cell activation in vitro in a concentration-dependent manner. Supplementary Figure 4. Detection of ERK phosphorylation in activated T cells. Supplementary Figure 5. Gating strategies for OT-1 and ex vivo phosphoflow. Supplementary Figure 6. PLX4720 enhances human T cell activation in vitro in a concentration-dependent manner.
Supplementary Figure 1 from Suboptimal T-cell Therapy Drives a Tumor Cell Mutator Phenotype That Promotes Escape from First-Line Treatment
Authors: Evgin Laura , Huff Amanda L. , Kottke Timothy , Thompson Jill , Molan Amy M. , Driscoll Christopher B. , Schuelke Matthew , Shim Kevin G. , Wongthida Phonphimon , Ilett Elizabeth J. , Smith Karen Kaluza , Harris Reuben S. , Coffey Matt , Pulido Jose S. , Pandha Hardev , Selby Peter J. , Harrington Kevin J. , Melcher Alan , Vile Richard G.
Published: April 2023

Suppl Fig1
Supplementary Figure 6 from Chimeric Antigen Receptor T Cells with Dissociated Signaling Domains Exhibit Focused Antitumor Activity with Reduced Potential for Toxicity In Vivo
Authors: Lanitis Evripidis , Poussin Mathilde , Klattenhoff Alex W. , Song Degang , Sandaltzopoulos Raphael , June Carl H. , Powell Daniel J.
Published: April 2023

PDF file - 583K, Figure S6. Trans-, but not cis-, signaling CART cells exhibit more limited in vitro activity against cells bearing single antigen. IFN-γ secretion by trans M-z/F-28 CART cells was significantly reduced in response to A1847M+/F- cells compared with parental A1847M+/F+. M-z, M-z/F-28, or M-28z transduced T cells (1 x 105 T cells) were cultured alone (none) or stimulated overnight with an equal number of C30, A1847M+/F+ or A1847M+/F- cells. Cell-free supernatant was harvested after ~20 hours of incubation and the IFN- γ levels were measure with ELISA. Mean IFN- γ concentration plus-minus SEM (pg/ml) from triplicate cultures is shown. *P < 0.05 comparing the IFN- γ secretion produced by M-z/F-28 CART cells against A1847M+/F+ versus A1847M+/F- cells.
Supplementary Figure 4 from Chimeric Antigen Receptor T Cells with Dissociated Signaling Domains Exhibit Focused Antitumor Activity with Reduced Potential for Toxicity In Vivo
Authors: Lanitis Evripidis , Poussin Mathilde , Klattenhoff Alex W. , Song Degang , Sandaltzopoulos Raphael , June Carl H. , Powell Daniel J.
Published: April 2023

PDF file - 514K, Figure S4. A1847 (M+/F+) and A1847 (M+/F-) cells exhibit similar in vitro growth rate. 1 x 106 A1847 (M+/F+) and A1847 (M+/F-) cells were seeded on day 0 and their in vitro growth kinetics were monitored by determining viable cells using the trypan blue exclusion method.
Figure S4 from Melanoma Sequentially Suppresses Different DC Subsets in the Sentinel Lymph Node, Affecting Disease Spread and Recurrence
Authors: van den Hout Mari F.C.M. , Koster Bas D. , Sluijter Berbel J.R. , Molenkamp Barbara G. , van de Ven Rieneke , van den Eertwegh Alfons J.M. , Scheper Rik J. , van Leeuwen Paul A.M. , van den Tol M. Petrousjka , de Gruijl Tanja D.
Published: April 2023

CD4+CD25hiFoxP3+ Treg rates in melanoma SLN, grouped by tumor stage
Supplementary Table 1 from Antigen-Specific Culture of Memory-like CD8 T Cells for Adoptive Immunotherapy
Authors: Litterman Adam J. , Zellmer David M. , LaRue Rebecca S. , Jameson Stephen C. , Largaespada David A.
Published: April 2023

XLSX - 35K, Supplementary Table 1. Upstream regulators predicted to be more activated in CD62L+CD44+ cocktail grown OT-I CD8 T cells versus sorted CD62L-CD44+ IL-2 grown OT-I CD8 T cells by transcriptional profiling.
Suppl fig 3 from Simultaneous Targeting of FcγRs and FcαRI Enhances Tumor Cell Killing
Authors: Brandsma Arianne M. , ten Broeke Toine , Nederend Maaike , Meulenbroek Laura A.P.M. , van Tetering Geert , Meyer Saskia , Jansen J.H. Marco , Beltrán Buitrago M. Alejandra , Nagelkerke Sietse Q. , Németh István , Ubink Ruud , Rouwendal Gerard , Lohse Stefan , Valerius Thomas , Leusen Jeanette H.W. , Boross Peter
Published: April 2023

FcR expression on effector cells. Expression of FcγR and FcαRI expression was measured by flow cytometry using mAbs specific for FcγRI (CD64, clone 10.1), FcγRIIa (CD32, clone IV.3), FcγRIII (CD16, clone 3G8) and FcαRI (CD89, clone A77). Effector cells were identified in leukocytes by the following surface markers: monocytes: CD14+CD16+, PMNs: CD16+ and NK cells: CD3-CD56+.
Supplementary Figure S2 from Rational Combination of Immunotherapies with Clinical Efficacy in Mice with Advanced Cancer
Authors: Bransi Ali , Salgado Oscar Camilo , Beffinger Michal , Milo Karim , Silina Karina , Yagita Hideo , Becher Burkhard , Knuth Alexander , van den Broek Maries
Published: April 2023

Tolerization of TCR-I cells in TRAMP mice.
Supplementary Data from Extracellular S100A9 Protein in Bone Marrow Supports Multiple Myeloma Survival by Stimulating Angiogenesis and Cytokine Secretion
Authors: De Veirman Kim , De Beule Nathan , Maes Ken , Menu Eline , De Bruyne Elke , De Raeve Hendrik , Fostier Karel , Moreaux Jérôme , Kassambara Alboukadel , Hose Dirk , Heusschen Roy , Eriksson Helena , Vanderkerken Karin , Van Valckenborgh Els
Published: April 2023

Supplementary data and figure legends
Supplementary Figures from Hypomethylation of the Treg-Specific Demethylated Region in FOXP3 Is a Hallmark of the Regulatory T-cell Subtype in Adult T-cell Leukemia
Authors: Shimazu Yayoi , Shimazu Yutaka , Hishizawa Masakatsu , Hamaguchi Masahide , Nagai Yuya , Sugino Noriko , Fujii Sumie , Kawahara Masahiro , Kadowaki Norimitsu , Nishikawa Hiroyoshi , Sakaguchi Shimon , Takaori-Kondo Akifumi
Published: April 2023

Supplementary Figure S1. Sorting strategy of primary ATL cells, Supplementary Figure S2. Methylation status of CTLA4 exon 2 and HELIOS intron 5, Supplementary Figure S3. Hypomethylation of the TSDR correlates with FOXP3 expression, Supplementary Figure S4. Comparison of other phenotypes of primary ATL cells by using flow cytometric analysis, Supplementary Figure S5. Analysis of cytokine secretion in primary ATL cells, Supplementary Figure S6. The mRNA expression level of CTLA4, HELIOS and EOS in primary ATL cells,Supplementary Figure S7. HTLV-1-infected cell lines with the hypomethylated TSDR showed suppressive function resembling Tregs,Supplementary Figure S8. The methylation status of the TSDR did not correlate with tax or HBZ expression in primary ATL cells, Supplementary Figure S9. Overall survival, Supplementary Figure S10. Subpopulation of FOXP3-positive ATL cells in female patients.
Supplementary Figure Legend from IL4 from T Follicular Helper Cells Downregulates Antitumor Immunity
Authors: Shirota Hidekazu , Klinman Dennis M. , Ito Shuku-ei , Ito Hiroyasu , Kubo Masato , Ishioka Chikashi
Published: April 2023

Supplementary Figure Legends
Supplementary Figure 3 from IL4 from T Follicular Helper Cells Downregulates Antitumor Immunity
Authors: Shirota Hidekazu , Klinman Dennis M. , Ito Shuku-ei , Ito Hiroyasu , Kubo Masato , Ishioka Chikashi
Published: April 2023

Supplementary Figure 3. Kinetics of surface marker expression by IL-4 producing cells from tumor draining LNs and surface marker in tumor infiltrated CD4 T cells.
Supplementary Figure 2 from IL4 from T Follicular Helper Cells Downregulates Antitumor Immunity
Authors: Shirota Hidekazu , Klinman Dennis M. , Ito Shuku-ei , Ito Hiroyasu , Kubo Masato , Ishioka Chikashi
Published: April 2023

Supplementary Figure 2. GATA3 or FoxP3 expression in IL-4-produced cells.