bluuebunny/crossref_metadata_2025 huggingface dataset:
Data from Effective Treatment of Established Bone Metastases Can Be Achieved by Combinatorial Osteoclast Blockade and Depletion of Granulocytic Subsets
Authors: Capietto Aude-Hélène , Lee Seunghyun , Clever David , Eul Emily , Ellis Haley , Ma Cynthia X. , Faccio Roberta
Published: April 2023

Abstract
Osteoclast (OC) blockade has been successful in reducing tumor growth in bone in preclinical settings, but antiresorptive drugs, such as zoledronic acid (ZA), fail to improve the overall survival rate of patients with bone metastasis despite ameliorating skeletal complications. To address this unmet clinical need, we interrogated what other cells modulated tumor growth in bone in addition to OCs. Because myeloid-derived suppressor cells (MDSC)—heterogeneous populations expressing CD11b, Ly6C, and Ly6G markers—originate in the bone marrow and promote tumor progression, we hypothesized that their accumulation hinders ZA antitumor effects. By using a murine model of bone metastasis insensitive to OC blockade, we assessed the antitumor effect of MDSC depletion using anti-Gr1 in mice bearing skeletal lung [Lewis lung carcinoma (LLC)], melanoma (B16-F10), and mammary (4T1) tumors. Differently from soft tissue tumors, anti-Gr1 did not reduce bone metastases and led to the paradoxical accumulation of bone marrow–resident CD11b+Ly6CintLy6Gint cells that differentiated into OCs when cultured in vitro. Anti-Gr1–mediated depletion of Ly6G+ granulocytic MDSCs combined with ZA-induced OC blockade reduced growth of established skeletal metastases compared with each agent alone. CD15+ granulocytic populations were increased in patients with breast cancer with progressive bone disease after antiresorptive treatment compared with those with stable bone disease. We provide evidence that antiresorptive therapies fail to reduce bone metastases in the presence of elevated granulocytic populations and that effective treatment of established skeletal metastases requires combinatorial depletion of granulocytes and OC blockade.
Data from Entinostat Decreases Immune Suppression to Promote Antitumor Responses in a HER2+ Breast Tumor Microenvironment
Authors: Sidiropoulos Dimitrios N. , Rafie Christine I. , Jang Julie K. , Castanon Sofi , Baugh Aaron G. , Gonzalez Edgar , Christmas Brian J. , Narumi Valerie H. , Davis-Marcisak Emily F. , Sharma Gaurav , Bigelow Emma , Vaghasia Ajay , Gupta Anuj , Skaist Alyza , Considine Michael , Wheelan Sarah J. , Ganesan Sathish Kumar , Yu Min , Yegnasubramanian Srinivasan , Stearns Vered , Connolly Roisin M. , Gaykalova Daria A. , Kagohara Luciane T. , Jaffee Elizabeth M. , Fertig Elana J. , Roussos Torres Evanthia T.
Published: April 2023

Abstract
Therapeutic combinations to alter immunosuppressive, solid tumor microenvironments (TME), such as in breast cancer, are essential to improve responses to immune checkpoint inhibitors (ICI). Entinostat, an oral histone deacetylase inhibitor, has been shown to improve responses to ICIs in various tumor models with immunosuppressive TMEs. The precise and comprehensive alterations to the TME induced by entinostat remain unknown. Here, we employed single-cell RNA sequencing on HER2-overexpressing breast tumors from mice treated with entinostat and ICIs to fully characterize changes across multiple cell types within the TME. This analysis demonstrates that treatment with entinostat induced a shift from a protumor to an antitumor TME signature, characterized predominantly by changes in myeloid cells. We confirmed myeloid-derived suppressor cells (MDSC) within entinostat-treated tumors associated with a less suppressive granulocytic (G)-MDSC phenotype and exhibited altered suppressive signaling that involved the NFκB and STAT3 pathways. In addition to MDSCs, tumor-associated macrophages were epigenetically reprogrammed from a protumor M2-like phenotype toward an antitumor M1-like phenotype, which may be contributing to a more sensitized TME. Overall, our in-depth analysis suggests that entinostat-induced changes on multiple myeloid cell types reduce immunosuppression and increase antitumor responses, which, in turn, improve sensitivity to ICIs. Sensitization of the TME by entinostat could ultimately broaden the population of patients with breast cancer who could benefit from ICIs.
Data from Intracellular Factor H Drives Tumor Progression Independently of the Complement Cascade
Authors: Daugan Marie V. , Revel Margot , Thouenon Romane , Dragon-Durey Marie-Agnès , Robe-Rybkine Tania , Torset Carine , Merle Nicolas S. , Noé Rémi , Verkarre Virginie , Oudard Stephane Marie , Mejean Arnaud , Validire Pierre , Cathelineau Xavier , Sanchez-Salas Rafael , Pickering Mathew C. , Cremer Isabelle , Mansuet-Lupo Audrey , Alifano Marco , Sautès-Fridman Catherine , Damotte Diane , Fridman Wolf H. , Roumenina Lubka T.
Published: April 2023

Abstract
The complement system is a powerful and druggable innate immune component of the tumor microenvironment. Nevertheless, it is challenging to elucidate the exact mechanisms by which complement affects tumor growth. In this study, we examined the processes by which the master complement regulator factor H (FH) affects clear cell renal cell carcinoma (ccRCC) and lung cancer, two cancers in which complement overactivation predicts poor prognosis. FH was present in two distinct cellular compartments: the membranous (mb-FH) and intracellular (int-FH) compartments. Int-FH resided in lysosomes and colocalized with C3. In ccRCC and lung adenocarcinoma, FH exerted protumoral action through an intracellular, noncanonical mechanism. FH silencing in ccRCC cell lines resulted in decreased proliferation, due to cell-cycle arrest and increased mortality, and this was associated with increased p53 phosphorylation and NFκB translocation to the nucleus. Moreover, the migration of the FH-silenced cells was reduced, likely due to altered morphology. These effects were cell type–specific because no modifications occurred upon CFH silencing in other FH-expressing cells tested: tubular cells (from which ccRCC originates), endothelial cells (human umbilical vein endothelial cells), and squamous cell lung cancer cells. Consistent with this, in ccRCC and lung adenocarcinoma, but not in lung squamous cell carcinoma, int-FH conferred poor prognosis in patient cohorts. Mb-FH performed its canonical function of complement regulation but had no impact on tumor cell phenotype or patient survival. The discovery of intracellular functions for FH redefines the role of the protein in tumor progression and its use as a prognostic biomarker or potential therapeutic target.

See article by Daugan et al., p. 891 (36).
Data from Comprehensive Characterizations of Immune Receptor Repertoire in Tumors and Cancer Immunotherapy Studies
Authors: Song Li , Ouyang Zhangyi , Cohen David , Cao Yang , Altreuter Jennifer , Bai Gali , Hu Xihao , Livak Kenneth J. , Li Heng , Tang Ming , Li Bo , Liu X. Shirley
Published: April 2023

Abstract
We applied our computational algorithm TRUST4 to assemble immune receptor (T-cell receptor/B-cell receptor) repertoires from approximately 12,000 RNA sequencing samples from The Cancer Genome Atlas and seven immunotherapy studies. From over 35 million assembled complete complementary-determining region 3 sequences, we observed that the expression of CCL5 and MZB1 is the most positively correlated genes with T-cell clonal expansion and B-cell clonal expansion, respectively. We analyzed amino acid evolution during B-cell receptor somatic hypermutation and identified tyrosine as the preferred residue. We found that IgG1+IgG3 antibodies together with FcRn were associated with complement-dependent cytotoxicity and antibody-dependent cellular cytotoxicity or phagocytosis. In addition to B-cell infiltration, we discovered that B-cell clonal expansion and IgG1+IgG3 antibodies are also correlated with better patient outcomes. Finally, we created a website, VisualizIRR, for users to interactively explore and visualize the immune repertoires in this study.

See related Spotlight by Liu and Han, p. 786
Data from A Multispecific Anti-CD40 DARPin Construct Induces Tumor-Selective CD40 Activation and Tumor Regression
Authors: Rigamonti Nicolò , Veitonmäki Niina , Domke Clara , Barsin Sophie , Jetzer Sarah , Abdelmotaleb Omar , Bessey Ralph , Lekishvili Tamara , Malvezzi Francesca , Gachechiladze Mariam , Behe Martin , Levitsky Victor , Trail Pamela A.
Published: April 2023

Abstract
The CD40 receptor is an attractive target for cancer immunotherapy. Although a modest pharmacodynamic effect is seen in patients following administration of CD40-targeting monoclonal antibodies (mAb), the doses that could be safely administered do not result in a meaningful clinical response, most likely due to the limited therapeutic window associated with systemic CD40 activation. To overcome this issue, we developed a multispecific DARPin construct, α-FAPxCD40, which has conditional activity at the site of disease. α-FAPxCD40 activation of CD40 depends on binding to fibroblast activation protein (FAP), a cell-surface protease overexpressed in the stroma of solid tumors. In vitro studies demonstrated that α-FAPxCD40 potently activates human antigen-presenting cells in the presence, but not in the absence, of FAP-positive cells. After intravenous injection, a murine surrogate construct (α-mFAPxCD40) accumulated in FAP-positive tumors, elicited rejection of 88% of these tumors, and induced memory antitumor immunity. Importantly, in contrast to the mouse anti-CD40 tested in parallel, the in vivo antitumor activity of α-mFAPxCD40 was associated neither with elevated blood cytokines nor with hepatotoxicity, both of which contribute to the clinical dose-limiting toxicities of several CD40 mAb. This study demonstrates that α-(m)FAPxCD40 engages CD40 in an FAP-restricted manner, leading to tumor eradication without signs of peripheral toxicity. This distinct preclinical profile suggests that a favorable therapeutic index may be achieved in humans. It further supports the development of α-FAPxCD40, currently tested in a first-in-human clinical study in patients with solid tumors (NCT05098405).
Data from P2RX7 Enhances Tumor Control by CD8+ T Cells in Adoptive Cell Therapy
Authors: Wanhainen Kelsey M. , Peng Changwei , Zhou Maggie H. , Macedo Bruna de Gois , O'Flanagan Stephen , Yang Tingyuan , Kelekar Ameeta , Burbach Brandon J. , Borges da Silva Henrique , Jameson Stephen C.
Published: April 2023

Abstract
Expression of the purinergic receptor P2RX7 by CD8+ T cells promotes the generation of memory populations following acute infections. However, data suggest that P2RX7 may limit the efficacy of antitumor responses. Herein, we show that P2RX7 is beneficial for optimal melanoma control in a mouse CD8+ T-cell adoptive transfer model. Tumor-specific P2rx7–/– CD8+ T cells exhibited impaired mitochondrial maintenance and function but did not display signs of overt exhaustion early in the antitumor response. However, as the tumor burden increased, the relative frequency of P2RX7-deficient CD8+ T cells declined within the tumor; this correlated with reduced proliferation, increased apoptosis, and mitochondrial dysfunction. Extending these studies, we found that the transient in vitro stimulation of P2RX7 using the ATP analogue BzATP led to enhanced B16 melanoma control by CD8+ T cells. These findings are in keeping with the concept that extracellular ATP (eATP) sensing by P2RX7 on CD8+ T cells is required for their ability to efficiently eliminate tumors by promoting mitochondrial fitness and underscore the potential for P2RX7 stimulation as a novel therapeutic treatment to enhance tumor immunotherapy.
Data from PD-1/PD-L1 Inhibition Enhances Chemotherapy-Induced Neuropathic Pain by Suppressing Neuroimmune Antinociceptive Signaling
Authors: Wanderley Carlos Wagner S. , Maganin Alexandre G.M. , Adjafre Beatriz , Mendes Atlante S. , Silva Conceição Elidianne Anibal , Quadros Andreza Urba , Luiz João Paulo Mesquita , Silva Camila Meirelles S. , Silva Nicole R. , Oliveira Francisco Fabio Bezerra , Gomes Francisco Isaac F. , Restrepo Jeferson Leandro J. , Speck-Hernandez Cesar A. , Turaça Fernanda , Silva Gabriel Victor Lucena , Pigatto Glauce R. , Nakaya Helder I. , Mota Jose Mauricio , Barroso-Sousa Romualdo , Alves-Filho José C. , Cunha Thiago M. , Cunha Fernando Q.
Published: April 2023

Abstract
Cytotoxic agents synergize with immune checkpoint inhibitors and improve outcomes for patients with several cancer types. Nonetheless, a parallel increase in the incidence of dose-limiting side effects, such as peripheral neuropathy, is often observed. Here, we investigated the role of the programmed cell death-1 (PD-1)/programmed death-ligand 1 (PD-L1) axis in the modulation of paclitaxel-induced neuropathic pain. We found that human and mouse neural tissues, including the dorsal root ganglion (DRG), expressed basal levels of PD-1 and PD-L1. During the development of paclitaxel-induced neuropathy, an increase in PD-L1 expression was observed in macrophages from the DRG. This effect depended on Toll-like receptor 4 activation by paclitaxel. Furthermore, PD-L1 inhibited pain behavior triggered by paclitaxel or formalin in mice, suggesting that PD-1/PD-L1 signaling attenuates peripheral neuropathy development. Consistent with this, we observed that the combined use of anti–PD-L1 plus paclitaxel increased mechanical allodynia and chronic neuropathy development induced by single agents. This effect was associated with higher expression of inflammatory markers (Tnf, Il6, and Cx3cr1) in peripheral nervous tissue. Together, these results suggest that PD-1/PD-L1 inhibitors enhance paclitaxel-induced neuropathic pain by suppressing PD-1/PD-L1 antinociceptive signaling.
Data from Activation of Tumor-Cell STING Primes NK-Cell Therapy
Authors: Knelson Erik H. , Ivanova Elena V. , Tarannum Mubin , Campisi Marco , Lizotte Patrick H. , Booker Matthew A. , Ozgenc Ismail , Noureddine Moataz , Meisenheimer Brittany , Chen Minyue , Piel Brandon , Spicer Nathaniel , Obua Bonje , Messier Cameron M. , Shannon Erin , Mahadevan Navin R. , Tani Tetsuo , Schol Pieter J. , Lee-Hassett Anna M. , Zlota Ari , Vo Ha V. , Ha Minh , Bertram Arrien A. , Han Saemi , Thai Tran C. , Gustafson Corinne E. , Venugopal Kartika , Haggerty Timothy J. , Albertson Thomas P. , Hartley Antja-Voy , Eser Pinar O. , Li Ze-Hua , Cañadas Israel , Vivero Marina , De Rienzo Assunta , Richards William G. , Abu-Yousif Adnan O. , Appleman Vicky A. , Gregory Richard C. , Parent Alexander , Lineberry Neil , Smith Eric L. , Jänne Pasi A. , Miret Juan J. , Tolstorukov Michael Y. , Romee Rizwan , Paweletz Cloud P. , Bueno Raphael , Barbie David A.
Published: April 2023

Abstract
Activation of the stimulator of interferon genes (STING) pathway promotes antitumor immunity but STING agonists have yet to achieve clinical success. Increased understanding of the mechanism of action of STING agonists in human tumors is key to developing therapeutic combinations that activate effective innate antitumor immunity. Here, we report that malignant pleural mesothelioma cells robustly express STING and are responsive to STING agonist treatment ex vivo. Using dynamic single-cell RNA sequencing of explants treated with a STING agonist, we observed CXCR3 chemokine activation primarily in tumor cells and cancer-associated fibroblasts, as well as T-cell cytotoxicity. In contrast, primary natural killer (NK) cells resisted STING agonist–induced cytotoxicity. STING agonists enhanced migration and killing of NK cells and mesothelin-targeted chimeric antigen receptor (CAR)-NK cells, improving therapeutic activity in patient-derived organotypic tumor spheroids. These studies reveal the fundamental importance of using human tumor samples to assess innate and cellular immune therapies. By functionally profiling mesothelioma tumor explants with elevated STING expression in tumor cells, we uncovered distinct consequences of STING agonist treatment in humans that support testing combining STING agonists with NK and CAR-NK cell therapies.
Data from Immuno-PET Monitoring of Lymphocytes Using the CD8-Specific Antibody REGN5054
Authors: Tavaré Richard , Danton Makenzie , Giurleo Jason T. , Makonnen Sosina , Hickey Carlos , Arnold Tomas C. , Kelly Marcus P. , Fredriksson Fanny , Bruestle Karina , Hermann Aynur , Ullman Erica , Edelmann Kurt H. , Potocky Terra , Dudgeon Drew , Bhatt Nikunj B. , Doubrovin Mikhail , Barry Thomas , Kyratsous Christos A. , Gurer Cagan , Tu Naxin , Gartner Hans , Murphy Andrew , Macdonald Lynn E. , Popke Jon , Mintz Akiva , Griesemer Adam , Olson William C. , Thurston Gavin , Ma Dangshe , Kirshner Jessica R.
Published: April 2023

Abstract
Assessment of immune-cell subsets within the tumor immune microenvironment is a powerful approach to better understand cancer immunotherapy responses. However, the use of biopsies to assess the tumor immune microenvironment poses challenges, including the potential for sampling error, restricted sampling over time, and inaccessibility of some tissues/organs, as well as the fact that single biopsy analyses do not reflect discordance across multiple intrapatient tumor lesions. Immuno-positron emission tomography (PET) presents a promising translational imaging approach to address the limitations and assess changes in the tumor microenvironment. We have developed 89Zr-DFO-REGN5054, a fully human CD8A-specific antibody conjugate, to assess CD8+ tumor-infiltrating lymphocytes (TIL) pre- and posttherapy. We used multiple assays, including in vitro T-cell activation, proliferation, and cytokine production, and in vivo viral clearance and CD8 receptor occupancy, to demonstrate that REGN5054 has minimal impact on T-cell activity. Preclinical immuno-PET studies demonstrated that 89Zr-DFO-REGN5054 specifically detected CD8+ T cells in lymphoid tissues of CD8-genetically humanized immunocompetent mice (VelociT mice) and discerned therapy-induced changes in CD8+ TILs in two models of response to a CD20xCD3 T-cell activating bispecific antibody (REGN1979, odronextamab). Toxicology studies in cynomolgus monkeys showed no overt toxicity, and immuno-PET imaging in cynomolgus monkeys demonstrated dose-dependent clearance and specific targeting to lymphoid tissues. This work supports the clinical investigation of 89Zr-DFO-REGN5054 to monitor T-cell responses in patients undergoing cancer immunotherapy.
Data from Tyrosine Kinase Inhibition Alters Intratumoral CD8+ T-cell Subtype Composition and Activity
Authors: Tieniber Andrew D. , Hanna Andrew N. , Medina Benjamin D. , Vitiello Gerardo A. , Etherington Mark S. , Liu Mengyuan , Do Kevin J. , Rossi Ferdinando , DeMatteo Ronald P.
Published: April 2023

Abstract
Targeted therapy with a tyrosine kinase inhibitor (TKI) such as imatinib is effective in treating gastrointestinal stromal tumor (GIST), but it is rarely curative. Despite the presence of a robust immune CD8+ T-cell infiltrate, combining a TKI with immune-checkpoint blockade (ICB) in advanced GIST has achieved only modest effects. To identify limitations imposed by imatinib on the antitumor immune response, we performed bulk RNA sequencing (RNA-seq), single-cell RNA-seq, and flow cytometry to phenotype CD8+ T-cell subsets in a genetically engineered mouse model of GIST. Imatinib reduced the frequency of effector CD8+ T cells and increased the frequency of naïve CD8+ T cells within mouse GIST, which coincided with altered tumor chemokine production, CD8+ T-cell recruitment, and reduced CD8+ T-cell intracellular PI3K signaling. Imatinib also failed to induce intratumoral T-cell receptor (TCR) clonal expansion. Consistent with these findings, human GISTs sensitive to imatinib harbored fewer effector CD8+ T cells but more naïve CD8+ T cells. Combining an IL15 superagonist (IL15SA) with imatinib restored intratumoral effector CD8+ T-cell function and CD8+ T-cell intracellular PI3K signaling, resulting in greater tumor destruction. Combination therapy with IL15SA and ICB resulted in the greatest tumor killing and maintained an effector CD8+ T-cell population in the presence of imatinib. Our findings highlight the impact of oncogene inhibition on intratumoral CD8+ T cells and support the use of agonistic T-cell therapy during TKI and/or ICB administration.
Data from NET-Triggered NLRP3 Activation and IL18 Release Drive Oxaliplatin-Induced Peripheral Neuropathy
Authors: Lin Tongtong , Hu Liang , Hu Fan , Li Kun , Wang Chao-Yu , Zong Li-Juan , Zhao Ya-Qian , Zhang Xiaotao , Li Yan , Yang Yang , Wang Yu , Jiang Chun-Yi , Wu Xuefeng , Liu Wen-Tao
Published: April 2023

Abstract
Oxaliplatin is an antineoplastic agent frequently used in the treatment of gastrointestinal tumors. However, it causes dose-limiting sensorimotor neuropathy, referred to as oxaliplatin-induced peripheral neuropathy (OIPN), for which there is no effective treatment. Here, we report that the elevation of neutrophil extracellular traps (NET) is a pathologic change common to both cancer patients treated with oxaliplatin and a murine model of OIPN. Mechanistically, we found that NETs trigger NLR family pyrin domain containing 3 (NLRP3) inflammasome activation and the subsequent release of IL18 by macrophages, resulting in mechanical hyperalgesia. In NLRP3-deficient mice, the mechanical hyperalgesia characteristic of OIPN in our model was reduced. In addition, in the murine model, treatment with the IL18 decoy receptor IL18BP prevented the development of OIPN. We further showed that eicosapentaenoic acid (EPA) reduced NET formation by suppressing the LPS–TLR4–JNK pathway and thereby abolished NLRP3 inflammasome activation and the subsequent secretion of IL18, which markedly prevented oxaliplatin-induced mechanical hyperalgesia in mice. These results identify a role for NET-triggered NLRP3 activation and IL18 release in the development of OIPN and suggest that utilizing IL18BP and EPA could be effective treatments for OIPN.
Data from CD73 Inhibits cGAS–STING and Cooperates with CD39 to Promote Pancreatic Cancer
Authors: Jacoberger-Foissac Célia , Cousineau Isabelle , Bareche Yacine , Allard David , Chrobak Pavel , Allard Bertrand , Pommey Sandra , Messaoudi Nouredin , McNicoll Yannic , Soucy Geneviève , Koseoglu Secil , Masia Ricard , Lake Andrew C. , Seo Heewon , Eeles Christopher B. , Rohatgi Neha , Robson Simon C. , Turcotte Simon , Haibe-Kains Benjamin , Stagg John
Published: April 2023

Abstract
The ectonucleotidases CD39 and CD73 catalyze extracellular ATP to immunosuppressive adenosine, and as such, represent potential cancer targets. We investigated biological impacts of CD39 and CD73 in pancreatic ductal adenocarcinoma (PDAC) by studying clinical samples and experimental mouse tumors. Stromal CD39 and tumoral CD73 expression significantly associated with worse survival in human PDAC samples and abolished the favorable prognostic impact associated with the presence of tumor-infiltrating CD8+ T cells. In mouse transplanted KPC tumors, both CD39 and CD73 on myeloid cells, as well as CD73 on tumor cells, promoted polarization of infiltrating myeloid cells towards an M2-like phenotype, which enhanced tumor growth. CD39 on tumor-specific CD8+ T cells and pancreatic stellate cells also suppressed IFNγ production by T cells. Although therapeutic inhibition of CD39 or CD73 alone significantly delayed tumor growth in vivo, targeting of both ectonucleotidases exhibited markedly superior antitumor activity. CD73 expression on human and mouse PDAC tumor cells also protected against DNA damage induced by gemcitabine and irradiation. Accordingly, large-scale pharmacogenomic analyses of human PDAC cell lines revealed significant associations between CD73 expression and gemcitabine chemoresistance. Strikingly, increased DNA damage in CD73-deficient tumor cells associated with activation of the cGAS–STING pathway. Moreover, cGAS expression in mouse KPC tumor cells was required for antitumor activity of the CD73 inhibitor AB680 in vivo. Our study, thus, illuminates molecular mechanisms whereby CD73 and CD39 seemingly cooperate to promote PDAC progression.
Data from Self-Renewing CD8+ T-cell Abundance in Blood Associates with Response to Immunotherapy
Authors: Maniar Rohan , Wang Peter H. , Washburn Robert S. , Kratchmarov Radomir , Coley Shana M. , Saqi Anjali , Pan Samuel S. , Hu Jianhua , Shu Catherine A. , Rizvi Naiyer A. , Henick Brian S. , Reiner Steven L.
Published: April 2023

Abstract
Treatment with immune checkpoint blockade (ICB) often fails to elicit durable antitumor immunity. Recent studies suggest that ICB does not restore potency to terminally dysfunctional T cells, but instead drives proliferation and differentiation of self-renewing progenitor T cells into fresh, effector-like T cells. Antitumor immunity catalyzed by ICB is characterized by mobilization of antitumor T cells in systemic circulation and tumor. To address whether abundance of self-renewing T cells in blood is associated with immunotherapy response, we used flow cytometry of peripheral blood from a cohort of patients with metastatic non–small cell lung cancer (NSCLC) treated with ICB. At baseline, expression of T-cell factor 1 (TCF1), a marker of self-renewing T cells, was detected at higher frequency in effector-memory (CCR7–) CD8+ T cells from patients who experienced durable clinical benefit compared to those with primary resistance to ICB. On-treatment blood samples from patients benefiting from ICB also exhibited a greater frequency of TCF1+CCR7–CD8+ T cells and higher proportions of TCF1 expression in treatment-expanded PD-1+CCR7–CD8+ T cells. The observed correlation of TCF1 frequency in CCR7–CD8+ T cells and response to ICB suggests that broader examination of self-renewing T-cell abundance in blood will determine its potential as a noninvasive, predictive biomarker of response and resistance to immunotherapy.
Supplementary Data from Sphingosine-1-Phosphate Receptor 3 Potentiates Inflammatory Programs in Normal and Leukemia Stem Cells to Promote Differentiation
Authors: Xie Stephanie Z. , Kaufmann Kerstin B. , Wang Weijia , Chan-Seng-Yue Michelle , Gan Olga I. , Laurenti Elisa , Garcia-Prat Laura , Takayanagi Shin-ichiro , Ng Stanley W.K. , Xu ChangJiang , Zeng Andy G.X. , Jin Liqing , McLeod Jessica , Wagenblast Elvin , Mitchell Amanda , Kennedy James A. , Liu Qiang , Boutzen Héléna , Kleinau Melissa , Jargstorf Joseph , Holmes Gareth , Zhang Yang , Voisin Veronique , Bader Gary D. , Wang Jean C.Y. , Hannun Yusuf A. , Luberto Chiara , Schroeder Timm , Minden Mark D. , Dick John E.
Published: April 2023

Supplemental Movie
Table S2 from Preneoplastic Alterations Define CLL DNA Methylome and Persist through Disease Progression and Therapy
Authors: Kretzmer Helene , Biran Anat , Purroy Noelia , Lemvigh Camilla K. , Clement Kendell , Gruber Michaela , Gu Hongcang , Rassenti Laura , Mohammad Arman W. , Lesnick Connie , Slager Susan L. , Braggio Esteban , Shanafelt Tait D. , Kay Neil E. , Fernandes Stacey M. , Brown Jennifer R. , Wang Lili , Li Shuqiang , Livak Kenneth J. , Neuberg Donna S. , Klages Sven , Timmermann Bernd , Kipps Thomas J. , Campo Elias , Gnirke Andreas , Wu Catherine J. , Meissner Alexander
Published: April 2023

List of DMRs and specifications between normal B cells and CLL as returned from the DMR caller
Table S1 from Preneoplastic Alterations Define CLL DNA Methylome and Persist through Disease Progression and Therapy
Authors: Kretzmer Helene , Biran Anat , Purroy Noelia , Lemvigh Camilla K. , Clement Kendell , Gruber Michaela , Gu Hongcang , Rassenti Laura , Mohammad Arman W. , Lesnick Connie , Slager Susan L. , Braggio Esteban , Shanafelt Tait D. , Kay Neil E. , Fernandes Stacey M. , Brown Jennifer R. , Wang Lili , Li Shuqiang , Livak Kenneth J. , Neuberg Donna S. , Klages Sven , Timmermann Bernd , Kipps Thomas J. , Campo Elias , Gnirke Andreas , Wu Catherine J. , Meissner Alexander
Published: April 2023

Cohort summary and details for CLL, MBL, and single cell samples
Figure S2 from Preneoplastic Alterations Define CLL DNA Methylome and Persist through Disease Progression and Therapy
Authors: Kretzmer Helene , Biran Anat , Purroy Noelia , Lemvigh Camilla K. , Clement Kendell , Gruber Michaela , Gu Hongcang , Rassenti Laura , Mohammad Arman W. , Lesnick Connie , Slager Susan L. , Braggio Esteban , Shanafelt Tait D. , Kay Neil E. , Fernandes Stacey M. , Brown Jennifer R. , Wang Lili , Li Shuqiang , Livak Kenneth J. , Neuberg Donna S. , Klages Sven , Timmermann Bernd , Kipps Thomas J. , Campo Elias , Gnirke Andreas , Wu Catherine J. , Meissner Alexander
Published: April 2023

Methylation landscape of CD5 positive and negative naïve and memory B cells is highly similar
Supplementary Data from Targeting MEF2D-fusion Oncogenic Transcriptional Circuitries in B-cell Precursor Acute Lymphoblastic Leukemia
Authors: Tsuzuki Shinobu , Yasuda Takahiko , Kojima Shinya , Kawazu Masahito , Akahane Koshi , Inukai Takeshi , Imaizumi Masue , Morishita Takanobu , Miyamura Koichi , Ueno Toshihide , Karnan Sivasundaram , Ota Akinobu , Hyodo Toshinori , Konishi Hiroyuki , Sanada Masashi , Nagai Hirokazu , Horibe Keizo , Tomita Akihiro , Suzuki Kyogo , Muramatsu Hideki , Takahashi Yoshiyuki , Miyazaki Yasushi , Matsumura Itaru , Kiyoi Hitoshi , Hosokawa Yoshitaka , Mano Hiroyuki , Hayakawa Fumihiko
Published: April 2023

SupplementaryFigures
Supplementary Data from Cytotoxic Therapy–Induced Effects on Both Hematopoietic and Marrow Stromal Cells Promotes Therapy-Related Myeloid Neoplasms
Authors: Stoddart Angela , Wang Jianghong , Fernald Anthony A. , Davis Elizabeth M. , Johnson Camille R. , Hu Chunmei , Cheng Jason X. , McNerney Megan E. , Le Beau Michelle M.
Published: April 2023

Supplemental Figures 1-7 and supplemental Tables 1-7
Supplementary Figures from PRPS-ST: A Protocol-Agnostic Self-training Method for Gene Expression–Based Classification of Blood Cancers
Authors: Jiang Aixiang , Hilton Laura K. , Tang Jeffrey , Rushton Christopher K. , Grande Bruno M. , Scott David W. , Morin Ryan D.
Published: April 2023

Supplementary Figures
Supplementary Data from NOT-Gated CD93 CAR T Cells Effectively Target AML with Minimized Endothelial Cross-Reactivity
Authors: Richards Rebecca M. , Zhao Feifei , Freitas Katherine A. , Parker Kevin R. , Xu Peng , Fan Amy , Sotillo Elena , Daugaard Mads , Oo Htoo Zarni , Liu Jie , Hong Wan-Jen , Sorensen Poul H. , Chang Howard Y. , Satpathy Ansuman T. , Majzner Robbie G. , Majeti Ravindra , Mackall Crystal L.
Published: April 2023

Supplemental figures and legends in one document
Supplementary Methods from ROBO1 Promotes Homing, Dissemination, and Survival of Multiple Myeloma within the Bone Marrow Microenvironment
Authors: Bianchi Giada , Czarnecki Peter G. , Ho Matthew , Roccaro Aldo M. , Sacco Antonio , Kawano Yawara , Gullà Annamaria , Samur Anil Aktas , Chen Tianzeng , Wen Kenneth , Tai Yu-Tzu , Moscvin Maria , Wu Xinchen , Camci-Unal Gulden , Da Vià Matteo C. , Bolli Niccolo' , Sewastianik Tomasz , Carrasco Ruben D. , Ghobrial Irene M. , Anderson Kenneth C.
Published: April 2023

Supplementary Methods
Supplementary Figure from Convergent Clonal Evolution of Signaling Gene Mutations Is a Hallmark of Myelodysplastic Syndrome Progression
Authors: Menssen Andrew J. , Khanna Ajay , Miller Christopher A. , Nonavinkere Srivatsan Sridhar , Chang Gue Su , Shao Jin , Robinson Joshua , O'Laughlin Michele , Fronick Catrina C. , Fulton Robert S. , Brendel Kimberly , Heath Sharon E. , Saba Raya , Welch John S. , Spencer David H. , Payton Jacqueline E. , Westervelt Peter , DiPersio John F. , Link Daniel C. , Schuelke Matthew J. , Jacoby Meagan A. , Duncavage Eric J. , Ley Timothy J. , Walter Matthew J.
Published: April 2023

Supplementary Figure from Convergent Clonal Evolution of Signaling Gene Mutations Is a Hallmark of Myelodysplastic Syndrome Progression
Supplementary Tables from In Vivo Modeling of CLL Transformation to Richter Syndrome Reveals Convergent Evolutionary Paths and Therapeutic Vulnerabilities
Authors: ten Hacken Elisa , Sewastianik Tomasz , Yin Shanye , Hoffmann Gabriela Brunsting , Gruber Michaela , Clement Kendell , Penter Livius , Redd Robert A. , Ruthen Neil , Hergalant Sébastien , Sholokhova Alanna , Fell Geoffrey , Parry Erin M. , Broséus Julien , Guieze Romain , Lucas Fabienne , Hernández-Sánchez María , Baranowski Kaitlyn , Southard Jackson , Joyal Heather , Billington Leah , Regis Fara Faye D. , Witten Elizabeth , Uduman Mohamed , Knisbacher Binyamin A. , Li Shuqiang , Lyu Haoxiang , Vaisitti Tiziana , Deaglio Silvia , Inghirami Giorgio , Feugier Pierre , Stilgenbauer Stephan , Tausch Eugen , Davids Matthew S. , Getz Gad , Livak Kenneth J. , Bozic Ivana , Neuberg Donna S. , Carrasco Ruben D. , Wu Catherine J.
Published: April 2023

Supplementary file contains all supplementary tables S1-S16 in Excel format in the order in which they appear in the text.
Data from Personalized Single-Cell Proteogenomics to Distinguish Acute Myeloid Leukemia from Nonmalignant Clonal Hematopoiesis
Authors: Dillon Laura W. , Ghannam Jack , Nosiri Chidera , Gui Gege , Goswami Meghali , Calvo Katherine R. , Lindblad Katherine E. , Oetjen Karolyn A. , Wilkerson Matthew D. , Soltis Anthony R. , Sukumar Gauthaman , Dalgard Clifton L. , Thompson Julie , Valdez Janet , DeStefano Christin B. , Lai Catherine , Sciambi Adam , Durruthy-Durruthy Robert , Llanso Aaron , Gulati Saurabh , Wang Shu , Ooi Aik , Dagur Pradeep K. , McCoy J. Philip , Burr Patrick , Li Yuesheng , Hourigan Christopher S.
Published: April 2023

Abstract
Genetic mutations associated with acute myeloid leukemia (AML) also occur in age-related clonal hematopoiesis, often in the same individual. This makes confident assignment of detected variants to malignancy challenging. The issue is particularly crucial for AML posttreatment measurable residual disease monitoring, where results can be discordant between genetic sequencing and flow cytometry. We show here that it is possible to distinguish AML from clonal hematopoiesis and to resolve the immunophenotypic identity of clonal architecture. To achieve this, we first design patient-specific DNA probes based on patient's whole-genome sequencing and then use them for patient-personalized single-cell DNA sequencing with simultaneous single-cell antibody–oligonucleotide sequencing. Examples illustrate AML arising from DNMT3A- and TET2-mutated clones as well as independently. The ability to personalize single-cell proteogenomic assessment for individual patients based on leukemia-specific genomic features has implications for ongoing AML precision medicine efforts.
Significance:
This study offers a proof of principle of patient-personalized customized single-cell proteogenomics in AML including whole-genome sequencing–defined structural variants, currently unmeasurable by commercial “off-the-shelf” panels. This approach allows for the definition of genetic and immunophenotype features for an individual patient that would be best suited for measurable residual disease tracking.
Data from Clonal Hematopoiesis Is Associated with Increased Risk of Severe Neurotoxicity in Axicabtagene Ciloleucel Therapy of Large B-Cell Lymphoma
Authors: Saini Neeraj Y. , Swoboda David M. , Greenbaum Uri , Ma Junsheng , Patel Romil D. , Devashish Kartik , Das Kaberi , Tanner Mark R. , Strati Paolo , Nair Ranjit , Fayad Luis , Ahmed Sairah , Lee Hun Ju , Iyer Swaminathan P. , Steiner Raphael , Jain Nitin , Nastoupil Loretta , Loghavi Sanam , Tang Guilin , Bassett Roland L. , Jain Preetesh , Wang Michael , Westin Jason R. , Green Michael R. , Sallman David A. , Padron Eric , Davila Marco L. , Locke Frederick L. , Champlin Richard E. , Garcia-Manero Guillermo , Shpall Elizabeth J. , Kebriaei Partow , Flowers Christopher R. , Jain Michael D. , Wang Feng , Futreal Andrew P. , Gillis Nancy , Neelapu Sattva S. , Takahashi Koichi
Published: April 2023

Abstract
To explore the role of clonal hematopoiesis (CH) in chimeric antigen receptor (CAR) T-cell therapy outcomes, we performed targeted deep sequencing on buffy coats collected during the 21 days before lymphodepleting chemotherapy from 114 large B-cell lymphoma patients treated with anti-CD19 CAR T cells. We detected CH in 42 (36.8%) pretreatment samples, most frequently in PPM1D (19/114) and TP53 (13/114) genes. Grade ≥3 immune effector cell-associated neurotoxicity syndrome (ICANS) incidence was higher in CH-positive patients than CH-negative patients (45.2% vs. 25.0%, P = 0.038). Higher toxicities with CH were primarily associated with DNMT3A, TET2, and ASXL1 genes (DTA mutations). Grade ≥3 ICANS (58.9% vs. 25%, P = 0.02) and ≥3 cytokine release syndrome (17.7% vs. 4.2%, P = 0.08) incidences were higher in DTA-positive than in CH-negative patients. The estimated 24-month cumulative incidence of therapy-related myeloid neoplasms after CAR T-cell therapy was higher in CH-positive than CH-negative patients [19% (95% CI, 5.5–38.7) vs. 4.2% (95% CI, 0.3–18.4), P = 0.028].
Significance:
Our study reveals that CH mutations, especially those associated with inflammation (DNMT3A, TET2, and ASXL1), are associated with severe-grade neurotoxicities in lymphoma patients receiving anti-CD19 CAR T-cell therapy. Further studies to investigate the mechanisms and interventions to improve toxicities in the context of CH are warranted.

See related content by Uslu and June, p. 382.

This article is highlighted in the In This Issue feature, p. 369
Data from Distinct Genetically Determined Origins of Myd88/BCL2-Driven Aggressive Lymphoma Rationalize Targeted Therapeutic Intervention Strategies
Authors: Flümann Ruth , Hansen Julia , Pelzer Benedikt W. , Nieper Pascal , Lohmann Tim , Kisis Ilmars , Riet Tobias , Kohlhas Viktoria , Nguyen Phuong-Hien , Peifer Martin , Abedpour Nima , Bosco Graziella , Thomas Roman K. , Kochanek Moritz , Knüfer Jacqueline , Jonigkeit Lorenz , Beleggia Filippo , Holzem Alessandra , Büttner Reinhard , Lohneis Philipp , Meinel Jörn , Ortmann Monika , Persigehl Thorsten , Hallek Michael , Calado Dinis Pedro , Chmielewski Markus , Klein Sebastian , Göthert Joachim R. , Chapuy Bjoern , Zevnik Branko , Wunderlich F. Thomas , von Tresckow Bastian , Jachimowicz Ron D. , Melnick Ari M. , Reinhardt Hans Christian , Knittel Gero
Published: April 2023

Abstract
Genomic profiling revealed the identity of at least 5 subtypes of diffuse large B-cell lymphoma (DLBCL), including the MCD/C5 cluster characterized by aberrations in MYD88, BCL2, PRDM1, and/or SPIB. We generated mouse models harboring B cell–specific Prdm1 or Spib aberrations on the background of oncogenic Myd88 and Bcl2 lesions. We deployed whole-exome sequencing, transcriptome, flow-cytometry, and mass cytometry analyses to demonstrate that Prdm1- or Spib-altered lymphomas display molecular features consistent with prememory B cells and light-zone B cells, whereas lymphomas lacking these alterations were enriched for late light-zone and plasmablast-associated gene sets. Consistent with the phenotypic evidence for increased B cell receptor signaling activity in Prdm1-altered lymphomas, we demonstrate that combined BTK/BCL2 inhibition displays therapeutic activity in mice and in five of six relapsed/refractory DLBCL patients. Moreover, Prdm1-altered lymphomas were immunogenic upon transplantation into immuno-competent hosts, displayed an actionable PD-L1 surface expression, and were sensitive to antimurine-CD19-CAR-T cell therapy, in vivo.
Significance:
Relapsed/refractory DLBCL remains a major medical challenge, and most of these patients succumb to their disease. Here, we generated mouse models, faithfully recapitulating the biology of MYD88-driven human DLBCL. These models revealed robust preclinical activity of combined BTK/BCL2 inhibition. We confirmed activity of this regimen in pretreated non–GCB-DLBCL patients.

See related commentary by Leveille et al., p. 8.

This article is highlighted in the In This Issue feature, p. 1
Supplementary Data S4 from Multiple germline events contribute to cancer development in patients with Li-Fraumeni syndrome
Authors: Subasri Vallijah , Light Nicholas , Kanwar Nisha , Brzezinski Jack , Luo Ping , Hansford Jordan R , Cairney Elizabeth , Portwine Carol , Elser Christine , Finlay Jonathan L. , Nichols Kim E. , Alon Noa , Brunga Ledia , Anson Jo , Kohlmann Wendy , de Andrade Kelvin C. , Khincha Payal P. , Savage Sharon A. , Schiffman Joshua D , Weksberg Rosanna , Pugh Trevor J. , Villani Anita , Shlien Adam , Goldenberg Anna , Malkin David
Published: April 2023

KiCS Variants
Supplement 8 from The Vaginal Microbiome is Associated with Endometrial Cancer Grade and Histology
Authors: Hakimjavadi Hesamedin , George Sophia H. , Taub Michael , Dodds Leah V. , Sanchez-Covarrubias Alex P. , Huang Marilyn , Pearson J. Matt , Slomovitz Brian M. , Kobetz Erin N. , Gharaibeh Raad , Sowamber Ramlogan , Pinto Andre , Chamala Srikar , Schlumbrecht Matthew P.
Published: April 2023

Functional pathway analysis
Supplement 1 from The Vaginal Microbiome is Associated with Endometrial Cancer Grade and Histology
Authors: Hakimjavadi Hesamedin , George Sophia H. , Taub Michael , Dodds Leah V. , Sanchez-Covarrubias Alex P. , Huang Marilyn , Pearson J. Matt , Slomovitz Brian M. , Kobetz Erin N. , Gharaibeh Raad , Sowamber Ramlogan , Pinto Andre , Chamala Srikar , Schlumbrecht Matthew P.
Published: April 2023

Additional statistical methods
Figure S7 from Inhibiting ERK5 Overcomes Breast Cancer Resistance to Anti-HER2 Therapy By Targeting the G1–S Cell-Cycle Transition
Authors: Zhang Jingwei , Pearson Adam J. , Sabherwal Nitin , Telfer Brian A. , Ali Nisha , Kan Karmern , Xu Qiuping , Zhang Wei , Chen Fuhui , Li Shiyang , Wang Jinhua , Gray Nathanael S. , Risa-Ebrí Blanca , Finegan Katherine G. , Cross Michael J. , Giurisato Emanuele , Whitmarsh Alan J. , Tournier Cathy
Published: April 2023

These data support the conclusion that ERK5 inhibtion enhances the cytostatic activity of lapatinib in resistance cells without increasing cytotoxicity.
Figure S5 from Inhibiting ERK5 Overcomes Breast Cancer Resistance to Anti-HER2 Therapy By Targeting the G1–S Cell-Cycle Transition
Authors: Zhang Jingwei , Pearson Adam J. , Sabherwal Nitin , Telfer Brian A. , Ali Nisha , Kan Karmern , Xu Qiuping , Zhang Wei , Chen Fuhui , Li Shiyang , Wang Jinhua , Gray Nathanael S. , Risa-Ebrí Blanca , Finegan Katherine G. , Cross Michael J. , Giurisato Emanuele , Whitmarsh Alan J. , Tournier Cathy
Published: April 2023

BT474, SK-BR-3, BT474-LR and MDA-MB-453 cell lines display distinct sensitivity to the apoptotic effect of 500 nM lapatinib.
Figure S4 from Inhibiting ERK5 Overcomes Breast Cancer Resistance to Anti-HER2 Therapy By Targeting the G1–S Cell-Cycle Transition
Authors: Zhang Jingwei , Pearson Adam J. , Sabherwal Nitin , Telfer Brian A. , Ali Nisha , Kan Karmern , Xu Qiuping , Zhang Wei , Chen Fuhui , Li Shiyang , Wang Jinhua , Gray Nathanael S. , Risa-Ebrí Blanca , Finegan Katherine G. , Cross Michael J. , Giurisato Emanuele , Whitmarsh Alan J. , Tournier Cathy
Published: April 2023

Both, sensitive and resistant HER2+ breast cancer cell lines exhibit impaired AKT phosphorylation following lapatinib treatment and increased ERK5 hyperphosphorylation following incubation with trametinib or PD0325901.
Figure S2 from Inhibiting ERK5 Overcomes Breast Cancer Resistance to Anti-HER2 Therapy By Targeting the G1–S Cell-Cycle Transition
Authors: Zhang Jingwei , Pearson Adam J. , Sabherwal Nitin , Telfer Brian A. , Ali Nisha , Kan Karmern , Xu Qiuping , Zhang Wei , Chen Fuhui , Li Shiyang , Wang Jinhua , Gray Nathanael S. , Risa-Ebrí Blanca , Finegan Katherine G. , Cross Michael J. , Giurisato Emanuele , Whitmarsh Alan J. , Tournier Cathy
Published: April 2023

The pattern of ERK5 expression was analyzed in normal breast and tumor tissues from a cohort of patients diagnosed with invasive ductal HER2+ carcinoma.
Supplementary Figures S1-S5 from TAK-676: A Novel Stimulator of Interferon Genes (STING) Agonist Promoting Durable IFN-dependent Antitumor Immunity in Preclinical Studies
Authors: Carideo Cunniff Elizabeth , Sato Yosuke , Mai Doanh , Appleman Vicky A. , Iwasaki Shinji , Kolev Vihren , Matsuda Atsushi , Shi Judy , Mochizuki Michiyo , Yoshikawa Masato , Huang Jian , Shen Luhua , Haridas Satyajeet , Shinde Vaishali , Gemski Chris , Roberts Emily R. , Ghasemi Omid , Bazzazi Hojjat , Menon Saurabh , Traore Tary , Shi Pu , Thelen Tennille D. , Conlon Joseph , Abu-Yousif Adnan O. , Arendt Christopher , Shaw Michael H. , Okaniwa Masanori
Published: April 2023

Supplementary figures: Supplementary Figure 1 shows cell viability of human monocyte-derived dendric cells and mouse bone marrow dendritic cells. Supplementary Figure 2 shows mean plasma and tumor concentration-time curves of TAK-676 in BALB/C mice (A20 syngeneic tumors). Supplementary Figure 3 shows percentage body weight change in BALB/C mice (CT26.WT and A20 syngeneic tumors). Supplementary Figure 4 shows percentage body weight change in STING-deficient Goldenticket mice (STING WT and B16F10 syngeneic tumors). Supplementary Figure 5 shows cytokine expression in A20 tumor-bearing mice (plasma and tumor).
Supplemental Table 5 from Race-associated Molecular Changes in Gynecologic Malignancies
Authors: Asare Amma , Yao Hui , Lara Olivia D. , Wang Ying , Zhang Lin , Sood Anil K.
Published: April 2023

Differentially methylated probes in Pan-Gyn cohort
Supplemental Figure S3 from Race-associated Molecular Changes in Gynecologic Malignancies
Authors: Asare Amma , Yao Hui , Lara Olivia D. , Wang Ying , Zhang Lin , Sood Anil K.
Published: April 2023

Expression levels of RNA-processing pathway members
Supplementary Fig S4 from Development of an Automated Liquid Biopsy Assay for Methylated Markers in Advanced Breast Cancer
Authors: Fackler Mary Jo , Tulac Suzana , Venkatesan Neesha , Aslam Adam J. , de Guzman Timothy N. , Mercado-Rodriguez Claudia , Cope Leslie M. , Downs Bradley M. , Vali Abdul Hussain , Ding Wanjun , Lehman Jennifer , Denbow Rita , Reynolds Jeffrey , Buckley Morgan E. , Visvanathan Kala , Umbricht Christopher B. , Wolff Antonio C. , Stearns Vered , Bates Michael , Lai Edwin W. , Sukumar Saraswati
Published: April 2023

Figure shows ACTB reference gene DNA levels plotted for each of the 132 study samples. Stage IV breast cancer patient sera had significantly higher total ACTB DNA (lower Ct) compared to normal (Mann Whitney P < 0.0001). Descriptive statistics are shown for normal vs. cancer and for methylation Cartridge A vs Cartridge B
Table S5 from A Phenogenetic Axis that Modulates Clinical Manifestation and Predicts Treatment Outcome in Primary Myeloid Neoplasms
Authors: Shen Qiujin , Feng Yahui , Gong Xiaowen , Jia Yujiao , Gao Qingyan , Jiao Xiaokang , Qi Saibing , Liu Xueou , Wei Hui , Huang Bingqing , Zhao Ningning , Song Xiaoqiang , Ma Yueshen , Liang Shihao , Zhang Donglei , Qin Li , Wang Ying , Qu Shiqiang , Zou Yao , Chen Yumei , Guo Ye , Yi Shuhua , An Gang , Jiao Zengtao , Zhang Song , Li Linfeng , Yan Jun , Wang Huijun , Song Zhen , Mi Yingchang , Qiu Lugui , Zhu Xiaofan , Wang Jianxiang , Xiao Zhijian , Chen Junren
Published: April 2023

Table S5. THAMP-Illumina-171 and the 27 benchmark gene panels.
Figures S1-S6, Tables S8-S10 from A Phenogenetic Axis that Modulates Clinical Manifestation and Predicts Treatment Outcome in Primary Myeloid Neoplasms
Authors: Shen Qiujin , Feng Yahui , Gong Xiaowen , Jia Yujiao , Gao Qingyan , Jiao Xiaokang , Qi Saibing , Liu Xueou , Wei Hui , Huang Bingqing , Zhao Ningning , Song Xiaoqiang , Ma Yueshen , Liang Shihao , Zhang Donglei , Qin Li , Wang Ying , Qu Shiqiang , Zou Yao , Chen Yumei , Guo Ye , Yi Shuhua , An Gang , Jiao Zengtao , Zhang Song , Li Linfeng , Yan Jun , Wang Huijun , Song Zhen , Mi Yingchang , Qiu Lugui , Zhu Xiaofan , Wang Jianxiang , Xiao Zhijian , Chen Junren
Published: April 2023

Figure S1. The most prevalent gene mutations and chromosomal abnormalities for AML in THAMP. Figure S2. The most prevalent gene mutations and chromosomal abnormalities for MDS in THAMP. Figure S3. The most prevalent gene mutations and chromosomal abnormalities for MDS/MPN in THAMP. Figure S4. The most prevalent gene mutations and chromosomal abnormalities for MPN in THAMP. Figure S5. Ranking order of genes along the Pan-Myeloid Axis. Figure S6. Ranking order of clinical features along the Pan-Myeloid Axis. Table S8. Clinical features in THAMP. Table S9. ELN risk stratification of AML patients in THAMP. Table S10. Classification and risk stratification of MDS patients in THAMP.