bluuebunny/crossref_metadata_2025 huggingface dataset:
Data from Somatic Superenhancer Duplications and Hotspot Mutations Lead to Oncogenic Activation of the KLF5 Transcription Factor
Authors: Zhang Xiaoyang , Choi Peter S. , Francis Joshua M. , Gao Galen F. , Campbell Joshua D. , Ramachandran Aruna , Mitsuishi Yoichiro , Ha Gavin , Shih Juliann , Vazquez Francisca , Tsherniak Aviad , Taylor Alison M. , Zhou Jin , Wu Zhong , Berger Ashton C. , Giannakis Marios , Hahn William C. , Cherniack Andrew D. , Meyerson Matthew
Published: April 2023

Abstract
The Krüppel-like family of transcription factors plays critical roles in human development and is associated with cancer pathogenesis. Krüppel-like factor 5 gene (KLF5) has been shown to promote cancer cell proliferation and tumorigenesis and to be genomically amplified in cancer cells. We recently reported that the KLF5 gene is also subject to other types of somatic coding and noncoding genomic alterations in diverse cancer types. Here, we show that these alterations activate KLF5 by three distinct mechanisms: (i) Focal amplification of superenhancers activates KLF5 expression in squamous cell carcinomas; (ii) Missense mutations disrupt KLF5–FBXW7 interactions to increase KLF5 protein stability in colorectal cancer; (iii) Cancer type–specific hotspot mutations within a zinc-finger DNA binding domain of KLF5 change its DNA binding specificity and reshape cellular transcription. Utilizing data from CRISPR/Cas9 gene knockout screening, we reveal that cancer cells with KLF5 overexpression are dependent on KLF5 for their proliferation, suggesting KLF5 as a putative therapeutic target.

Significance: Our observations, together with previous studies that identified oncogenic properties of KLF5, establish the importance of KLF5 activation in human cancers, delineate the varied genomic mechanisms underlying this occurrence, and nominate KLF5 as a putative target for therapeutic intervention in cancer. Cancer Discov; 8(1); 108–25. ©2017 AACR.

This article is highlighted in the In This Issue feature, p. 1
Data from ID1 Mediates Escape from TGFβ Tumor Suppression in Pancreatic Cancer
Authors: Huang Yun-Han , Hu Jing , Chen Fei , Lecomte Nicolas , Basnet Harihar , David Charles J. , Witkin Matthew D. , Allen Peter J. , Leach Steven D. , Hollmann Travis J. , Iacobuzio-Donahue Christine A. , Massagué Joan
Published: April 2023

Abstract
TGFβ is an important tumor suppressor in pancreatic ductal adenocarcinoma (PDA), yet inactivation of TGFβ pathway components occurs in only half of PDA cases. TGFβ cooperates with oncogenic RAS signaling to trigger epithelial-to-mesenchymal transition (EMT) in premalignant pancreatic epithelial progenitors, which is coupled to apoptosis owing to an imbalance of SOX4 and KLF5 transcription factors. We report that PDAs that develop with the TGFβ pathway intact avert this apoptotic effect via ID1. ID1 family members are expressed in PDA progenitor cells and encode components of a set of core transcriptional regulators shared by PDAs. PDA progression selects against TGFβ-mediated repression of ID1. The sustained expression of ID1 uncouples EMT from apoptosis in PDA progenitors. AKT signaling and mechanisms linked to low-frequency genetic events converge on ID1 to preserve its expression in PDA. Our results identify ID1 as a crucial node and potential therapeutic target in PDA.
Significance:
Half of PDAs escape TGFβ-induced tumor suppression without inactivating the TGFβ pathway. We report that ID1 expression is selected for in PDAs and that ID1 uncouples TGFβ-induced EMT from apoptosis. ID1 thus emerges as a crucial regulatory node and a target of interest in PDA.

This article is highlighted in the In This Issue feature, p. 1
Data from Type I Interferon Regulates a Coordinated Gene Network to Enhance Cytotoxic T Cell–Mediated Tumor Killing
Authors: Fan Jun-Bao , Miyauchi Sayuri , Xu Hui-Zhong , Liu Dan , Kim Leo J.Y. , Burkart Christoph , Cheng Hua , Arimoto Kei-ichiro , Yan Ming , Zhou Yu , Győrffy Balázs , Knobeloch Klaus-Peter , Rich Jeremy N. , Cang Hu , Fu Xiang-Dong , Zhang Dong-Er
Published: April 2023

Abstract
Type I interferons (IFN), which activate many IFN-stimulated genes (ISG), are known to regulate tumorigenesis. However, little is known regarding how various ISGs coordinate with one another in developing antitumor effects. Here, we report that the ISG UBA7 is a tumor suppressor in breast cancer. UBA7 encodes an enzyme that catalyzes the covalent conjugation of the ubiquitin-like protein product of another ISG (ISG15) to cellular proteins in a process known as “ISGylation.” ISGylation of other ISGs, including STAT1 and STAT2, synergistically facilitates production of chemokine-receptor ligands to attract cytotoxic T cells. These gene-activation events are further linked to clustering and nuclear relocalization of STAT1/2 within IFN-induced promyelocytic leukemia (PML) bodies. Importantly, this coordinated ISG–ISGylation network plays a central role in suppressing murine breast cancer growth and metastasis, which parallels improved survival in patients with breast cancer. These findings reveal a cooperative IFN-inducible gene network in orchestrating a tumor-suppressive microenvironment.
Significance:
We report a highly cooperative ISG network, in which UBA7-mediated ISGylation facilitates clustering of transcription factors and activates an antitumor gene-expression program. These findings provide mechanistic insights into immune evasion in breast cancer associated with UBA7 loss, emphasizing the importance of a functional ISG–ISGylation network in tumor suppression.

This article is highlighted in the In This Issue feature, p. 327
Data from The TP53 Apoptotic Network Is a Primary Mediator of Resistance to BCL2 Inhibition in AML Cells
Authors: Nechiporuk Tamilla , Kurtz Stephen E. , Nikolova Olga , Liu Tingting , Jones Courtney L. , D'Alessandro Angelo , Culp-Hill Rachel , d'Almeida Amanda , Joshi Sunil K. , Rosenberg Mara , Tognon Cristina E. , Danilov Alexey V. , Druker Brian J. , Chang Bill H. , McWeeney Shannon K , Tyner Jeffrey W.
Published: April 2023

Abstract
To study mechanisms underlying resistance to the BCL2 inhibitor venetoclax in acute myeloid leukemia (AML), we used a genome-wide CRISPR/Cas9 screen to identify gene knockouts resulting in drug resistance. We validated TP53, BAX, and PMAIP1 as genes whose inactivation results in venetoclax resistance in AML cell lines. Resistance to venetoclax resulted from an inability to execute apoptosis driven by BAX loss, decreased expression of BCL2, and/or reliance on alternative BCL2 family members such as BCL2L1. The resistance was accompanied by changes in mitochondrial homeostasis and cellular metabolism. Evaluation of TP53 knockout cells for sensitivities to a panel of small-molecule inhibitors revealed a gain of sensitivity to TRK inhibitors. We relate these observations to patient drug responses and gene expression in the Beat AML dataset. Our results implicate TP53, the apoptotic network, and mitochondrial functionality as drivers of venetoclax response in AML and suggest strategies to overcome resistance.
Significance:
AML is challenging to treat due to its heterogeneity, and single-agent therapies have universally failed, prompting a need for innovative drug combinations. We used a genetic approach to identify genes whose inactivation contributes to drug resistance as a means of forming preferred drug combinations to improve AML treatment.

See related commentary by Savona and Rathmell, p. 831.

This article is highlighted in the In This Issue feature, p. 813
Data from Altered Nuclear Export Signal Recognition as a Driver of Oncogenesis
Authors: Taylor Justin , Sendino Maria , Gorelick Alexander N. , Pastore Alessandro , Chang Matthew T. , Penson Alexander V. , Gavrila Elena I. , Stewart Connor , Melnik Ella M. , Herrejon Chavez Florisela , Bitner Lillian , Yoshimi Akihide , Lee Stanley Chun-Wei , Inoue Daichi , Liu Bo , Zhang Xiao J. , Mato Anthony R. , Dogan Ahmet , Kharas Michael G. , Chen Yuhong , Wang Demin , Soni Rajesh K. , Hendrickson Ronald C. , Prieto Gorka , Rodriguez Jose A. , Taylor Barry S. , Abdel-Wahab Omar
Published: April 2023

Abstract
Altered expression of XPO1, the main nuclear export receptor in eukaryotic cells, has been observed in cancer, and XPO1 has been a focus of anticancer drug development. However, mechanistic evidence for cancer-specific alterations in XPO1 function is lacking. Here, genomic analysis of 42,793 cancers identified recurrent and previously unrecognized mutational hotspots in XPO1. XPO1 mutations exhibited striking lineage specificity, with enrichment in a variety of B-cell malignancies, and introduction of single amino acid substitutions in XPO1 initiated clonal, B-cell malignancy in vivo. Proteomic characterization identified that mutant XPO1 altered the nucleocytoplasmic distribution of hundreds of proteins in a sequence-specific manner that promoted oncogenesis. XPO1 mutations preferentially sensitized cells to inhibitors of nuclear export, providing a biomarker of response to this family of drugs. These data reveal a new class of oncogenic alteration based on change-of-function mutations in nuclear export signal recognition and identify therapeutic targets based on altered nucleocytoplasmic trafficking.
Significance:
Here, we identify that heterozygous mutations in the main nuclear exporter in eukaryotic cells, XPO1, are positively selected in cancer and promote the initiation of clonal B-cell malignancies. XPO1 mutations alter nuclear export signal recognition in a sequence-specific manner and sensitize cells to compounds in clinical development inhibiting XPO1 function.

This article is highlighted in the In This Issue feature, p. 1325
Data from Simultaneous Inhibition of LSD1 and TGFβ Enables Eradication of Poorly Immunogenic Tumors with Anti–PD-1 Treatment
Authors: Sheng Wanqiang , Liu Yi , Chakraborty Damayanti , Debo Brian , Shi Yang
Published: April 2023

Abstract
Epigenetic regulators are a class of promising targets in combination with immune checkpoint inhibitors for cancer treatment, but the impact of the broad effects of perturbing epigenetic regulators on tumor immunotherapy remains to be fully explored. Here we show that ablation of the histone demethylase LSD1 in multiple tumor cells induces TGFβ expression, which exerts an inhibitory effect on T-cell immunity through suppressing the cytotoxicity of intratumoral CD8+ T cells and consequently dampens the antitumor effect of LSD1 ablation–induced T-cell infiltration. Importantly, concurrent depletion of LSD1 and TGFβ in combination with PD-1 blockade significantly increases both CD8+ T-cell infiltration and cytotoxicity, leading to eradication of poorly immunogenic tumors and a long-term protection from tumor rechallenge. Thus, combining LSD1 inhibition with blockade of TGFβ and PD-1 may represent a promising triple combination therapy for treating certain refractory tumors.
SignIficance:
Cotargeting LSD1 and TGFβ cooperatively elevates intratumoral CD8+ T-cell infiltration and unleashes their cytotoxicity, leading to tumor eradication upon anti–PD-1 treatment. Our findings illustrate a duality of epigenetic perturbations in immunotherapy and implicate the combination of LSD1 inhibition with dual PD-1/TGFβ blockade in treating certain poorly immunogenic tumors.

This article is highlighted in the In This Issue feature, p. 1861
Data from Bacterial-Driven Inflammation and Mutant BRAF Expression Combine to Promote Murine Colon Tumorigenesis That Is Sensitive to Immune Checkpoint Therapy
Authors: DeStefano Shields Christina E. , White James R. , Chung Liam , Wenzel Alyssa , Hicks Jessica L. , Tam Ada J. , Chan June L. , Dejea Christine M. , Fan Hongni , Michel John , Maiuri Ashley R. , Sriramkumar Shruthi , Podicheti Ram , Rusch Douglas B. , Wang Hao , De Marzo Angelo M. , Besharati Sepideh , Anders Robert A. , Baylin Stephen B. , O'Hagan Heather M. , Housseau Franck , Sears Cynthia L.
Published: April 2023

Abstract
Colorectal cancer is multifaceted, with subtypes defined by genetic, histologic, and immunologic features that are potentially influenced by inflammation, mutagens, and/or microbiota. Colorectal cancers with activating mutations in BRAF are associated with distinct clinical characteristics, although the pathogenesis is not well understood. The Wnt-driven multiple intestinal neoplasia (MinApcΔ716/+) enterotoxigenic Bacteroides fragilis (ETBF) murine model is characterized by IL17-dependent, distal colon adenomas. Herein, we report that the addition of the BRAFV600E mutation to this model results in the emergence of a distinct locus of midcolon tumors. In ETBF-colonized BRAFV600ELgr5CreMin (BLM) mice, tumors have similarities to human BRAFV600E tumors, including histology, CpG island DNA hypermethylation, and immune signatures. In comparison to Min ETBF tumors, BLM ETBF tumors are infiltrated by CD8+ T cells, express IFNγ signatures, and are sensitive to anti–PD-L1 treatment. These results provide direct evidence for critical roles of host genetic and microbiota interactions in colorectal cancer pathogenesis and sensitivity to immunotherapy.
Significance:
Colorectal cancers with BRAF mutations have distinct characteristics. We present evidence of specific colorectal cancer gene–microbial interactions in which colonization with toxigenic bacteria drives tumorigenesis in BRAFV600ELgr5CreMin mice, wherein tumors phenocopy aspects of human BRAF-mutated tumors and have a distinct IFNγ-dominant immune microenvironment uniquely responsive to immune checkpoint blockade.

This article is highlighted in the In This Issue feature, p. 1601
Data from Bacterial Genotoxin Accelerates Transient Infection–Driven Murine Colon Tumorigenesis
Authors: Liu Yue , Fu Kai , Wier Eric M. , Lei Yifan , Hodgson Andrea , Xu Dongqing , Xia Xue , Zheng Dandan , Ding Hua , Sears Cynthia L. , Yang Jian , Wan Fengyi
Published: April 2023

Abstract
Chronic and low-grade inflammation associated with persistent bacterial infections has been linked to colon tumor development; however, the impact of transient and self-limited infections in bacterially driven colon tumorigenesis has remained enigmatic. Here we report that UshA is a novel genotoxin in attaching/effacing (A/E) pathogens, which include the human pathogens enteropathogenic Escherichia coli, enterohemorrhagic E. coli, and their murine equivalent Citrobacter rodentium (CR). UshA harbors direct DNA digestion activity with a catalytic histidine–aspartic acid dyad. Injected via the type III secretion system (T3SS) into host cells, UshA triggers DNA damage and initiates tumorigenic transformation during infections in vitro and in vivo. Moreover, UshA plays an indispensable role in CR infection–accelerated colon tumorigenesis in genetically susceptible ApcMinΔ716/+ mice. Collectively, our results reveal that UshA, functioning as a bacterial T3SS-dependent genotoxin, plays a critical role in prompting transient and noninvasive bacterial infection–accelerated colon tumorigenesis in mice.
Significance:
We identified UshA, a novel T3SS-dependent genotoxin in A/E pathogens that possesses direct DNA digestion activity and confers bacterially accelerated colon tumorigenesis in mice. Our results demonstrate that acute and noninvasive infection with A/E pathogens harbors a far-reaching impact on the development of colon cancer.

This article is highlighted in the In This Issue feature, p. 1
Data from Loss of Optineurin Drives Cancer Immune Evasion via Palmitoylation-Dependent IFNGR1 Lysosomal Sorting and Degradation
Authors: Du Wan , Hua Fang , Li Xiong , Zhang Jian , Li Shasha , Wang Weichao , Zhou Jiajia , Wang Weimin , Liao Peng , Yan Yijian , Li Gaopeng , Wei Shuang , Grove Sara , Vatan Linda , Zgodziński Witold , Majewski Marek , Wallner Grzegorz , Chen Haoyan , Kryczek Ilona , Fang Jing-Yuan , Zou Weiping
Published: April 2023

Abstract
Mutations in IFN and MHC signaling genes endow immunotherapy resistance. Patients with colorectal cancer infrequently exhibit IFN and MHC signaling gene mutations and are generally resistant to immunotherapy. In exploring the integrity of IFN and MHC signaling in colorectal cancer, we found that optineurin was a shared node between the two pathways and predicted colorectal cancer patient outcome. Loss of optineurin occurs in early-stage human colorectal cancer. Immunologically, optineurin deficiency was shown to attenuate IFNGR1 and MHC-I expression, impair T-cell immunity, and diminish immunotherapy efficacy in murine cancer models and patients with cancer. Mechanistically, we observed that IFNGR1 was S-palmitoylated on Cys122, and AP3D1 bound with and sorted palmitoylated IFNGR1 to lysosome for degradation. Unexpectedly, optineurin interacted with AP3D1 to prevent palmitoylated IFNGR1 lysosomal sorting and degradation, thereby maintaining IFNγ and MHC-I signaling integrity. Furthermore, pharmacologically targeting IFNGR1 palmitoylation stabilized IFNGR1, augmented tumor immunity, and sensitized checkpoint therapy. Thus, loss of optineurin drives immune evasion and intrinsic immunotherapy resistance in colorectal cancer.
Significance:
Loss of optineurin impairs the integrity of both IFNγ and MHC-I signaling pathways via palmitoylation-dependent IFNGR1 lysosomal sorting and degradation, thereby driving immune evasion and intrinsic immunotherapy resistance in colorectal cancer. Our work suggests that pharmacologically targeting IFNGR1 palmitoylation can stabilize IFNGR1, enhance T-cell immunity, and sensitize checkpoint therapy in colorectal cancer.

See related commentary by Salvagno and Cubillos-Ruiz, p. 1623.

This article is highlighted in the In This Issue feature, p. 1601
Data from Exploiting Allosteric Properties of RAF and MEK Inhibitors to Target Therapy-Resistant Tumors Driven by Oncogenic BRAF Signaling
Authors: Adamopoulos Christos , Ahmed Tamer A. , Tucker Maxwell R. , Ung Peter M.U. , Xiao Min , Karoulia Zoi , Amabile Angelo , Wu Xuewei , Aaronson Stuart A. , Ang Celina , Rebecca Vito W. , Brown Brian D. , Schlessinger Avner , Herlyn Meenhard , Wang Qi , Shaw David E. , Poulikakos Poulikos I.
Published: April 2023

Abstract
Current clinical RAF inhibitors (RAFi) inhibit monomeric BRAF (mBRAF) but are less potent against dimeric BRAF (dBRAF). RAFi equipotent for mBRAF and dBRAF have been developed but are predicted to have lower therapeutic index. Here we identify a third class of RAFi that selectively inhibits dBRAF over mBRAF. Molecular dynamic simulations reveal restriction of the movement of the BRAF αC-helix as the basis of inhibitor selectivity. Combination of inhibitors based on their conformation selectivity (mBRAF- plus dBRAF-selective plus the most potent BRAF–MEK disruptor MEK inhibitor) promoted suppression of tumor growth in BRAFV600E therapy–resistant models. Strikingly, the triple combination showed no toxicities, whereas dBRAF-selective plus MEK inhibitor treatment caused weight loss in mice. Finally, the triple combination achieved durable response and improved clinical well-being in a patient with stage IV colorectal cancer. Thus, exploiting allosteric properties of RAF and MEK inhibitors enables the design of effective and well-tolerated therapies for BRAFV600E tumors.
Significance:
This work identifies a new class of RAFi that are selective for dBRAF over mBRAF and determines the basis of their selectivity. A rationally designed combination of RAF and MEK inhibitors based on their conformation selectivity achieved increased efficacy and a high therapeutic index when used to target BRAFV600E tumors.

See related commentary by Zhang and Bollag, p. 1620.

This article is highlighted in the In This Issue feature, p. 1601
Data from Mobocertinib (TAK-788): A Targeted Inhibitor of EGFR Exon 20 Insertion Mutants in Non–Small Cell Lung Cancer
Authors: Gonzalvez Francois , Vincent Sylvie , Baker Theresa E. , Gould Alexandra E. , Li Shuai , Wardwell Scott D. , Nadworny Sara , Ning Yaoyu , Zhang Sen , Huang Wei-Sheng , Hu Yongbo , Li Feng , Greenfield Matthew T. , Zech Stephan G. , Das Biplab , Narasimhan Narayana I. , Clackson Tim , Dalgarno David , Shakespeare William C. , Fitzgerald Michael , Chouitar Johara , Griffin Robert J. , Liu Shengwu , Wong Kwok-kin , Zhu Xiaotian , Rivera Victor M.
Published: April 2023

Abstract
Most EGFR exon 20 insertion (EGFRex20ins) driver mutations in non–small cell lung cancer (NSCLC) are insensitive to approved EGFR tyrosine kinase inhibitors (TKI). To address the limitations of existing therapies targeting EGFR-mutated NSCLC, mobocertinib (TAK-788), a novel irreversible EGFR TKI, was specifically designed to potently inhibit oncogenic variants containing activating EGFRex20ins mutations with selectivity over wild-type EGFR. The in vitro and in vivo activity of mobocertinib was evaluated in engineered and patient-derived models harboring diverse EGFRex20ins mutations. Mobocertinib inhibited viability of various EGFRex20ins-driven cell lines more potently than approved EGFR TKIs and demonstrated in vivo antitumor efficacy in patient-derived xenografts and murine orthotopic models. These findings support the ongoing clinical development of mobocertinib for the treatment of EGFRex20ins-mutated NSCLC.
Significance:
No oral EGFR-targeted therapies are approved for EGFR exon 20 insertion (EGFRex20ins) mutation-driven NSCLC. Mobocertinib is a novel small-molecule EGFR inhibitor specifically designed to target EGFRex20ins mutants. Preclinical data reported here support the clinical development of mobocertinib in patients with NSCLC with EGFR exon 20 insertion mutations.

See related commentary by Pacheco, p. 1617.

This article is highlighted in the In This Issue feature, p. 1601
Data from Tumor Microenvironment–Derived R-spondins Enhance Antitumor Immunity to Suppress Tumor Growth and Sensitize for Immune Checkpoint Blockade Therapy
Authors: Tang Yuting , Xu Qian , Hu Liang , Yan Xiaomei , Feng Xiaomin , Yokota Asumi , Wang Weinan , Zhan Di , Krishnamurthy Durga , Ochayon David E. , Wen Lijun , Huo Li , Zeng Huimin , Luo Yingwan , Huang L. Frank , Wunderlich Mark , Zhang Jiwang , Vivier Eric , Zhou Jianfeng , Waggoner Stephen N. , Huang Gang
Published: April 2023

Abstract
Natural killer (NK) cells and T cells are key effectors of antitumor immune responses and major targets of checkpoint inhibitors. In multiple cancer types, we find that the expression of Wnt signaling potentiator R-spondin genes (e.g., RSPO3) is associated with favorable prognosis and positively correlates with gene signatures of both NK cells and T cells. Although endothelial cells and cancer-associated fibroblasts comprise the R-spondin 3–producing cells, NK cells and T cells correspondingly express the R-spondin 3 receptor LGR6 within the tumor microenvironment (TME). Exogenous expression or intratumor injection of R-spondin 3 in tumors enhanced the infiltration and function of cytotoxic effector cells, which led to tumor regression. NK cells and CD8+ T cells independently and cooperatively contributed to R-spondin 3–induced control of distinct tumor types. The effect of R-spondin 3 was mediated in part through upregulation of MYC and ribosomal biogenesis. Importantly, R-spondin 3 expression enhanced tumor sensitivity to anti–PD-1 therapy, thereby highlighting new therapeutic avenues.
Significance:
Our study identifies novel targets in enhancing antitumor immunity and sensitizing immune checkpoint inhibition, which provides a rationale for developing new immunotherapies against cancers. It also offers mechanistic insights on Wnt signaling–mediated modulation of anticancer immunity in the TME and implications for a putative R-spondin–LGR6 axis in regulating NK-cell biology.

This article is highlighted in the In This Issue feature, p. 2945
Data from INK4 Tumor Suppressor Proteins Mediate Resistance to CDK4/6 Kinase Inhibitors
Authors: Li Qing , Jiang Baishan , Guo Jiaye , Shao Hong , Del Priore Isabella S. , Chang Qing , Kudo Rei , Li Zhiqiang , Razavi Pedram , Liu Bo , Boghossian Andrew S. , Rees Matthew G. , Ronan Melissa M. , Roth Jennifer A. , Donovan Katherine A. , Palafox Marta , Reis-Filho Jorge S. , de Stanchina Elisa , Fischer Eric S. , Rosen Neal , Serra Violeta , Koff Andrew , Chodera John D. , Gray Nathanael S. , Chandarlapaty Sarat
Published: April 2023

Abstract
Cyclin-dependent kinases 4 and 6 (CDK4/6) represent a major therapeutic vulnerability for breast cancer. The kinases are clinically targeted via ATP competitive inhibitors (CDK4/6i); however, drug resistance commonly emerges over time. To understand CDK4/6i resistance, we surveyed over 1,300 breast cancers and identified several genetic alterations (e.g., FAT1, PTEN, or ARID1A loss) converging on upregulation of CDK6. Mechanistically, we demonstrate CDK6 causes resistance by inducing and binding CDK inhibitor INK4 proteins (e.g., p18INK4C). In vitro binding and kinase assays together with physical modeling reveal that the p18INK4C–cyclin D–CDK6 complex occludes CDK4/6i binding while only weakly suppressing ATP binding. Suppression of INK4 expression or its binding to CDK6 restores CDK4/6i sensitivity. To overcome this constraint, we developed bifunctional degraders conjugating palbociclib with E3 ligands. Two resulting lead compounds potently degraded CDK4/6, leading to substantial antitumor effects in vivo, demonstrating the promising therapeutic potential for retargeting CDK4/6 despite CDK4/6i resistance.
Significance:
CDK4/6 kinase activation represents a common mechanism by which oncogenic signaling induces proliferation and is potentially targetable by ATP competitive inhibitors. We identify a CDK6–INK4 complex that is resilient to current-generation inhibitors and develop a new strategy for more effective inhibition of CDK4/6 kinases.

This article is highlighted in the In This Issue feature, p. 275
Data from MET Amplification Attenuates Lung Tumor Response to Immunotherapy by Inhibiting STING
Authors: Zhang Yong , Yang Qifan , Zeng Xiangyu , Wang Manxiang , Dong Shuang , Yang Bin , Tu Xinyi , Wei Ting , Xie Wenzhuan , Zhang Chao , Guo Qiang , Kloeber Jake A. , Cao Yueyu , Guo Guijie , Zhou Qin , Zhao Fei , Huang Jinzhou , Liu Li , Zhang Kai , Wang Mingwei , Yin Ping , Luo Kuntian , Deng Min , Kim Wootae , Hou Jing , Shi Yu , Zhu Qian , Chen Lifeng , Hu Sheng , Yue Junqiu , Pi Guoliang , Lou Zhenkun
Published: April 2023

Abstract
Immune checkpoint blockade (ICB) has revolutionized cancer therapy. However, the response of patients to ICB is difficult to predict. Here, we examined 81 patients with lung cancer under ICB treatment and found that patients with MET amplification were resistant to ICB and had a poor progression-free survival. Tumors with MET amplifications had significantly decreased STING levels and antitumor T-cell infiltration. Furthermore, we performed deep single-cell RNA sequencing on more than 20,000 single immune cells and identified an immunosuppressive signature with increased subsets of XIST- and CD96-positive exhausted natural killer (NK) cells and decreased CD8+ T-cell and NK-cell populations in patients with MET amplification. Mechanistically, we found that oncogenic MET signaling induces phosphorylation of UPF1 and downregulates tumor cell STING expression via modulation of the 3′-UTR length of STING by UPF1. Decreased efficiency of ICB by MET amplification can be overcome by inhibiting MET.
Significance:
We suggest that the combination of MET inhibitor together with ICB will overcome ICB resistance induced by MET amplification. Our report reveals much-needed information that will benefit the treatment of patients with primary MET amplification or EGFR–tyrosine kinase inhibitor resistant-related MET amplification.

This article is highlighted in the In This Issue feature, p. 2659
Data from Proteomic Screens for Suppressors of Anoikis Identify IL1RAP as a Promising Surface Target in Ewing Sarcoma
Authors: Zhang Hai-Feng , Hughes Christopher S. , Li Wei , He Jian-Zhong , Surdez Didier , El-Naggar Amal M. , Cheng Hongwei , Prudova Anna , Delaidelli Alberto , Negri Gian Luca , Li Xiaojun , Ørum-Madsen Maj Sofie , Lizardo Michael M. , Oo Htoo Zarni , Colborne Shane , Shyp Taras , Scopim-Ribeiro Renata , Hammond Colin A. , Dhez Anne-Chloe , Langman Sofya , Lim Jonathan K.M. , Kung Sonia H.Y. , Li Amy , Steino Anne , Daugaard Mads , Parker Seth J. , Geltink Ramon I. Klein , Orentas Rimas J. , Xu Li-Yan , Morin Gregg B. , Delattre Olivier , Dimitrov Dimiter S. , Sorensen Poul H.
Published: April 2023

Abstract
Cancer cells must overcome anoikis (detachment-induced death) to successfully metastasize. Using proteomic screens, we found that distinct oncoproteins upregulate IL1 receptor accessory protein (IL1RAP) to suppress anoikis. IL1RAP is directly induced by oncogenic fusions of Ewing sarcoma, a highly metastatic childhood sarcoma. IL1RAP inactivation triggers anoikis and impedes metastatic dissemination of Ewing sarcoma cells. Mechanistically, IL1RAP binds the cell-surface system Xc− transporter to enhance exogenous cystine uptake, thereby replenishing cysteine and the glutathione antioxidant. Under cystine depletion, IL1RAP induces cystathionine gamma lyase (CTH) to activate the transsulfuration pathway for de novo cysteine synthesis. Therefore, IL1RAP maintains cyst(e)ine and glutathione pools, which are vital for redox homeostasis and anoikis resistance. IL1RAP is minimally expressed in pediatric and adult normal tissues, and human anti-IL1RAP antibodies induce potent antibody-dependent cellular cytotoxicity of Ewing sarcoma cells. Therefore, we define IL1RAP as a new cell-surface target in Ewing sarcoma, which is potentially exploitable for immunotherapy.
Significance:
Here, we identify cell-surface protein IL1RAP as a key driver of metastasis in Ewing sarcoma, a highly aggressive childhood sarcoma. Minimal expression in pediatric and adult normal tissues nominates IL1RAP as a promising target for immunotherapy.

See related commentary by Yoon and DeNicola, p. 2679.

This article is highlighted in the In This Issue feature, p. 2659
Data from Sunvozertinib, a Selective EGFR Inhibitor for Previously Treated Non–Small Cell Lung Cancer with EGFR Exon 20 Insertion Mutations
Authors: Wang Mengzhao , Yang James Chih-Hsin , Mitchell Paul L. , Fang Jian , Camidge D. Ross , Nian Weiqi , Chiu Chao-Hua , Zhou Jianying , Zhao Yanqiu , Su Wu-Chou , Yang Tsung-Ying , Zhu Viola W. , Millward Michael , Fan Yun , Huang Wen-Tsung , Cheng Ying , Jiang Liyan , Brungs Daniel , Bazhenova Lyudmila , Lee Chee Khoon , Gao Bo , Xu Yan , Hsu Wei-Hsun , Zheng Li , Jänne Pasi A.
Published: April 2023

Abstract
Epidermal growth factor receptor exon 20 insertion mutations (EGFRexon20ins) are detected in approximately 2% of patients with non–small cell lung cancer (NSCLC). Due to a lack of effective therapy, the prognosis of these patients is typically poor. Sunvozertinib (DZD9008) was designed as an oral, potent, irreversible, and selective EGFR tyrosine kinase inhibitor, showing activity against EGFRexon20ins and other mutations. In both cell lines and xenograft models, sunvozertinib shows potent antitumor activity. In the two ongoing phase I clinical studies, sunvozertinib was tolerated up to 400 mg once daily. The most common drug-related adverse events included diarrhea and skin rash. Antitumor efficacy was observed at the doses of 100 mg and above in patients with EGFRexon20ins NSCLC across different subtypes, with prior amivantamab treatment as well as with baseline brain metastasis. The median duration of response has not been reached.
Significance:
We report the discovery and early clinical development of sunvozertinib, a potential treatment option for the unmet medical need of EGFRexon20ins NSCLC.

This article is highlighted in the In This Issue feature, p. 1599
Data from Sex-Biased ZRSR2 Mutations in Myeloid Malignancies Impair Plasmacytoid Dendritic Cell Activation and Apoptosis
Authors: Togami Katsuhiro , Chung Sun Sook , Madan Vikas , Booth Christopher A.G. , Kenyon Christopher M. , Cabal-Hierro Lucia , Taylor Justin , Kim Sunhee S. , Griffin Gabriel K. , Ghandi Mahmoud , Li Jia , Li Yvonne Y. , Angelot-Delettre Fanny , Biichle Sabeha , Seiler Michael , Buonamici Silvia , Lovitch Scott B. , Louissaint Abner , Morgan Elizabeth A. , Jardin Fabrice , Piccaluga Pier Paolo , Weinstock David M. , Hammerman Peter S. , Yang Henry , Konopleva Marina , Pemmaraju Naveen , Garnache-Ottou Francine , Abdel-Wahab Omar , Koeffler H. Phillip , Lane Andrew A.
Published: April 2023

Abstract
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an aggressive leukemia of plasmacytoid dendritic cells (pDC). BPDCN occurs at least three times more frequently in men than in women, but the reasons for this sex bias are unknown. Here, studying genomics of primary BPDCN and modeling disease-associated mutations, we link acquired alterations in RNA splicing to abnormal pDC development and inflammatory response through Toll-like receptors. Loss-of-function mutations in ZRSR2, an X chromosome gene encoding a splicing factor, are enriched in BPDCN, and nearly all mutations occur in males. ZRSR2 mutation impairs pDC activation and apoptosis after inflammatory stimuli, associated with intron retention and inability to upregulate the transcription factor IRF7. In vivo, BPDCN-associated mutations promote pDC expansion and signatures of decreased activation. These data support a model in which male-biased mutations in hematopoietic progenitors alter pDC function and confer protection from apoptosis, which may impair immunity and predispose to leukemic transformation.
Significance:
Sex bias in cancer is well recognized, but the underlying mechanisms are incompletely defined. We connect X chromosome mutations in ZRSR2 to an extremely male-predominant leukemia. Aberrant RNA splicing induced by ZRSR2 mutation impairs dendritic cell inflammatory signaling, interferon production, and apoptosis, revealing a sex- and lineage-related tumor suppressor pathway.

This article is highlighted in the In This Issue feature, p. 275
Data from Plasticity of Extrachromosomal and Intrachromosomal BRAF Amplifications in Overcoming Targeted Therapy Dosage Challenges
Authors: Song Kai , Minami Jenna K. , Huang Arthur , Dehkordi Siavash R. , Lomeli Shirley H. , Luebeck Jens , Goodman Mark H. , Moriceau Gatien , Krijgsman Oscar , Dharanipragada Prashanthi , Ridgley Trevor , Crosson William P. , Salazar Jesus , Pazol Eli , Karin Gabriel , Jayaraman Rachana , Balanis Nikolas G. , Alhani Salwan , Sheu Kyle , ten Hoeve Johanna , Palermo Amelia , Motika Stephen E. , Senaratne T. Niroshi , Paraiso Kim H. , Hergenrother Paul J. , Rao P. Nagesh , Multani Asha S. , Peeper Daniel S. , Bafna Vineet , Lo Roger S. , Graeber Thomas G.
Published: April 2023

Abstract
Focal amplifications (FA) can mediate targeted therapy resistance in cancer. Understanding the structure and dynamics of FAs is critical for designing treatments that overcome plasticity-mediated resistance. We developed a melanoma model of dual MAPK inhibitor (MAPKi) resistance that bears BRAFV600 amplifications through either extrachromosomal DNA (ecDNA)/double minutes (DM) or intrachromosomal homogenously staining regions (HSR). Cells harboring BRAFV600E FAs displayed mode switching between DMs and HSRs, from both de novo genetic changes and selection of preexisting subpopulations. Plasticity is not exclusive to ecDNAs, as cells harboring HSRs exhibit drug addiction–driven structural loss of BRAF amplicons upon dose reduction. FA mechanisms can couple with kinase domain duplications and alternative splicing to enhance resistance. Drug-responsive amplicon plasticity is observed in the clinic and can involve other MAPK pathway genes, such as RAF1 and NRAS. BRAF FA-mediated dual MAPKi–resistant cells are more sensitive to proferroptotic drugs, extending the spectrum of ferroptosis sensitivity in MAPKi resistance beyond cases of dedifferentiation.
Significance:
Understanding the structure and dynamics of oncogene amplifications is critical for overcoming tumor relapse. BRAF amplifications are highly plastic under MAPKi dosage challenges in melanoma, through involvement of de novo genomic alterations, even in the HSR mode. Moreover, BRAF FA-driven, dual MAPKi–resistant cells extend the spectrum of resistance-linked ferroptosis sensitivity.

This article is highlighted in the In This Issue feature, p. 873
Figure S4 from Macrophages and CD8+ T Cells Mediate the Antitumor Efficacy of Combined CD40 Ligation and Imatinib Therapy in Gastrointestinal Stromal Tumors
Authors: Zhang Jennifer Q. , Zeng Shan , Vitiello Gerardo A. , Seifert Adrian M. , Medina Benjamin D. , Beckman Michael J. , Loo Jennifer K. , Santamaria-Barria Juan , Maltbaek Joanna H. , Param Nesteene J. , Moral John A. , Zhao Julia N. , Balachandran Vinod , Rossi Ferdinand , Antonescu Cristina R. , DeMatteo Ronald P.
Published: April 2023

IM then CD40 treatment
Figure S1-S8 from Eradication of Hepatocellular Carcinoma by NKG2D-Based CAR-T Cells
Authors: Sun Bin , Yang Dong , Dai Hongjiu , Liu Xiuyun , Jia Ru , Cui Xiaoyue , Li Wenxuan , Cai Changchun , Xu Jianming , Zhao Xudong
Published: April 2023

Figure S1. NKG2DL levels in 50 pairs of normal tissues (N) and liver cancers (T). Data was obtained from The Cancer Genome Atlas (TCGA) database. Statistical differences were analyzed using paired Student's t-tests, *P {less than or equal to} 0.05, **P {less than or equal to} 0.01, ***P {less than or equal to} 0.001. Figure S2. Immunohistochemical analysis was performed to detect the expression of MICA and ULBP2 in Normal (N1-N4), Cirrhosis (C1-C7) and tumors (T) tissue, scale bar = 100 μm. Figure S3. T cells were isolated from peripheral blood using the RosetteSep{trade mark, serif} Human T Cell Enrichment Cocktail and the cell-surface expression of CD3 was analyzed by flow cytometry. The RAJI cell line was used as a negative control. Figure S4. SMMC7721 cells were cells infected with plko-shcoo2, plko-shMICA, and plko-shULBP2 lentivirus. Quantitative RT-PCR analysis showing the efficiency of MICA and ULBP2 knockdown in SMMC7721 cells. The shMICA-2# and shULBP2-2# was used to construct SMMC7721-shMICA and SMMC7721-shULBP2 cell lines, respectively. shCOO2 was used as negative control. The data are presented as the means {plus minus} SD. Figure S5. Growth curves of T cells isolated from healthy donor, patient 1 and patient 2. The data are presented as the means {plus minus} SD. P< 0.05 for the indicated cells. Figure S6. Flow cytometry analysis of the expression of CD19 and NKG2D CAR in transduced T cells isolated from healthy donor, patient 1 and patient 2. Figure S7. Proportions of CD4+ and CD8+ T cells in NTD, CD19-BBz CAR-T, and NKG2D-BBz CAR-T cells by flow cytometry. Figure S8. Proliferation (A) and apoptosis (B) of CD19-BBz CAR-T and NKG2D-BBz CAR-T cells at day 11 after transduction. The data are presented in as the means {plus minus} SD, ns, not significant.
Figure S1 from Inhibition of the NKp44-PCNA Immune Checkpoint Using a mAb to PCNA
Authors: Kundu Kiran , Ghosh Susmita , Sarkar Rhitajit , Edri Avishay , Brusilovsky Michael , Gershoni-Yahalom Orly , Yossef Rami , Shemesh Avishai , Soria Jean-Charles , Lazar Vladimir , Joshua Ben-Zion , Campbell Kerry S. , Elkabets Moshe , Porgador Angel
Published: April 2023

14-25-9 recognizes specifically PCNA on cancer cell membrane.
Supplementary Data from The Atypical Receptor CCRL2 Is Essential for Lung Cancer Immune Surveillance
Authors: Del Prete Annalisa , Sozio Francesca , Schioppa Tiziana , Ponzetta Andrea , Vermi William , Calza Stefano , Bugatti Mattia , Salvi Valentina , Bernardini Giovanni , Benvenuti Federica , Vecchi Annunciata , Bottazzi Barbara , Mantovani Alberto , Sozzani Silvano
Published: April 2023

Supplementary Figures
Supplementary Table 1 from A Genetic Screen to Identify Gain- and Loss-of-Function Modifications that Enhance T-cell Infiltration into Tumors
Authors: Rogers Laura M. , Wang Zhaoming , Mott Sarah L. , Dupuy Adam J. , Weiner George J.
Published: April 2023

Combined screen demographics
Source Data from A Genetic Screen to Identify Gain- and Loss-of-Function Modifications that Enhance T-cell Infiltration into Tumors
Authors: Rogers Laura M. , Wang Zhaoming , Mott Sarah L. , Dupuy Adam J. , Weiner George J.
Published: April 2023

This file contains all individual mapped insertion sites used as input for gCIS analysis, formatted as a .gff3 file.
Supplementary Table 3 from Immunologic Recognition of a Shared p53 Mutated Neoantigen in a Patient with Metastatic Colorectal Cancer
Authors: Lo Winifred , Parkhurst Maria , Robbins Paul F. , Tran Eric , Lu Yong-Chen , Jia Li , Gartner Jared J. , Pasetto Anna , Deniger Drew , Malekzadeh Parisa , Shelton Thomas E. , Prickett Todd , Ray Satyajit , Kivitz Scott , Paria Biman C. , Kriley Isaac , Schrump David S. , Rosenberg Steven A.
Published: April 2023

Supplementary Table 3
Supplementary Tables from Interferon-Induced IDO1 Mediates Radiation Resistance and Is a Therapeutic Target in Colorectal Cancer
Authors: Chen Baosheng , Alvarado David M. , Iticovici Micah , Kau Nathan S. , Park Haeseong , Parikh Parag J. , Thotala Dinesh , Ciorba Matthew A.
Published: April 2023

Supplementary Tables
Supplementary Figures and Legends 1-4 from CCR2-Dependent Recruitment of Tregs and Monocytes Following Radiotherapy Is Associated with TNFα-Mediated Resistance
Authors: Mondini Michele , Loyher Pierre-Louis , Hamon Pauline , Gerbé de Thoré Marine , Laviron Marie , Berthelot Kevin , Clémenson Céline , Salomon Benoit L. , Combadière Christophe , Deutsch Eric , Boissonnas Alexandre
Published: April 2023

Four supplementary figures and their legends.
Table S1 from T-cell Receptors Engineered De Novo for Peptide Specificity Can Mediate Optimal T-cell Activity without Self Cross-Reactivity
Authors: Sharma Preeti , Harris Daniel T. , Stone Jennifer D. , Kranz David M.
Published: April 2023

Supplementary Table S1: Predicted HLA-A2 binding MART-1 homologues present in human and mouse proteomes.
Supplementary Data from Macrophage-Targeted Therapy Unlocks Antitumoral Cross-talk between IFNγ-Secreting Lymphocytes and IL12-Producing Dendritic Cells
Authors: Pfirschke Christina , Zilionis Rapolas , Engblom Camilla , Messemaker Marius , Zou Angela E. , Rickelt Steffen , Gort-Freitas Nicolas A. , Lin Yunkang , Bill Ruben , Siwicki Marie , Gungabeesoon Jeremy , Sprachman Melissa M. , Marquard Angela N. , Rodell Christopher B. , Cuccarese Michael F. , Quintana Jeremy , Ahmed Maaz S. , Kohler Rainer H. , Savova Virginia , Weissleder Ralph , Klein Allon M. , Pittet Mikael J.
Published: April 2023

Supplementary Data from Macrophage-Targeted Therapy Unlocks Antitumoral Cross-talk between IFNγ-Secreting Lymphocytes and IL12-Producing Dendritic Cells
Supplementary Data from B7-H3 Suppresses Antitumor Immunity via the CCL2–CCR2–M2 Macrophage Axis and Contributes to Ovarian Cancer Progression
Authors: Miyamoto Taito , Murakami Ryusuke , Hamanishi Junzo , Tanigaki Kenji , Hosoe Yuko , Mise Nathan , Takamatsu Shiro , Mise Yuka , Ukita Masayo , Taki Mana , Yamanoi Koji , Horikawa Naoki , Abiko Kaoru , Yamaguchi Ken , Baba Tsukasa , Matsumura Noriomi , Mandai Masaki
Published: April 2023

Supplementary Data from B7-H3 Suppresses Antitumor Immunity via the CCL2–CCR2–M2 Macrophage Axis and Contributes to Ovarian Cancer Progression
Supplementary Figure from Circadian Regulator CLOCK Drives Immunosuppression in Glioblastoma
Authors: Xuan Wenjing , Hsu Wen-Hao , Khan Fatima , Dunterman Madeline , Pang Lizhi , Wainwright Derek A. , Ahmed Atique U. , Heimberger Amy B. , Lesniak Maciej S. , Chen Peiwen
Published: April 2023

Supplementary Figure from Circadian Regulator CLOCK Drives Immunosuppression in Glioblastoma
Supplementary Data from Visualizing Spatial and Stoichiometric Barriers to Bispecific T-Cell Engager Efficacy
Authors: You Ran , Artichoker Jordan , Ray Arja , Gonzalez Velozo Hugo , Rock Dan A. , Conner Kip P. , Krummel Matthew F.
Published: April 2023

Supplementary Data from Visualizing Spatial and Stoichiometric Barriers to Bispecific T-Cell Engager Efficacy
Movie S2 from CAR T-cell Entry into Tumor Islets Is a Two-Step Process Dependent on IFNγ and ICAM-1
Authors: Kantari-Mimoun Chahrazade , Barrin Sarah , Vimeux Lene , Haghiri Sandrine , Gervais Claire , Joaquina Sandy , Mittelstaet Joerg , Mockel-Tenbrinck Nadine , Kinkhabwala Ali , Damotte Diane , Lupo Audrey , Sibony Mathilde , Alifano Marco , Dondi Elisabetta , Bercovici Nadège , Trautmann Alain , Kaiser Andrew D. , Donnadieu Emmanuel
Published: April 2023

Ca2+ responses of Fluo-4-loaded CD20 CAR T cells introduced into a slice made from a Raji tumor
Supplementary Figure 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

Supplementary Figure from A Multispecific Anti-CD40 DARPin Construct Induces Tumor-Selective CD40 Activation and Tumor Regression
Supplementary Figure 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

Supplementary Figure from P2RX7 Enhances Tumor Control by CD8+ T Cells in Adoptive Cell Therapy
Video 3 from BET Inhibition Enhances TNF-Mediated Antitumor Immunity
Authors: Wellinger Lisa C. , Hogg Simon J. , Newman Dane M. , Friess Thomas , Geiss Daniela , Michie Jessica , Ramsbottom Kelly M. , Bacac Marina , Fauti Tanja , Marbach Daniel , Jarassier Laura , Thienger Phillip , Paehler Axel , Cluse Leonie A. , Kearney Conor J. , Vervoort Stephin J. , Trapani Joseph A. , Oliaro Jane , Shortt Jake , Ruefli-Brasse Astrid , Rohle Daniel , Johnstone Ricky W.
Published: April 2023

Supp Video 3
Supplementary Table from Single-Cell Analysis of the Pan-Cancer Immune Microenvironment and scTIME Portal
Authors: Hong Fang , Meng Qianqian , Zhang Weiyu , Zheng Ruiqin , Li Xiaoyun , Cheng Tao , Hu Deqing , Gao Xin
Published: April 2023

Supplementary Table from Single-Cell Analysis of the Pan-Cancer Immune Microenvironment and scTIME Portal
Supplementary Table 3 from β2-Integrin Adhesion Regulates Dendritic Cell Epigenetic and Transcriptional Landscapes to Restrict Dendritic Cell Maturation and Tumor Rejection
Authors: Guenther Carla , Faisal Imrul , Fusciello Manlio , Sokolova Maria , Harjunpää Heidi , Ilander Mette , Tallberg Robert , Vartiainen Maria Kristina , Alon Ronen , Gonzalez-Granado Jose-Maria , Cerullo Vincenzo , Fagerholm Susanna Carola
Published: April 2023

Supplementary Table 3
Supplementary Figure from Molecular Subgroups of Intrahepatic Cholangiocarcinoma Discovered by Single-Cell RNA Sequencing–Assisted Multiomics Analysis
Authors: Bao Xuanwen , Li Qiong , Chen Jinzhang , Chen Diyu , Ye Chanqi , Dai Xiaomeng , Wang Yanfang , Li Xin , Rong Xiaoxiang , Cheng Fei , Jiang Ming , Zhu Zheng , Ding Yongfeng , Sun Rui , Liu Chuan , Huang Lingling , Jin Yuzhi , Li Bin , Lu Juan , Wu Wei , Guo Yixuan , Fu Wenguang , Langley Sarah Raye , Tano Vincent , Fang Weijia , Guo Tiannan , Sheng Jianpeng , Zhao Peng , Ruan Jian
Published: April 2023

Supplementary Figure from Molecular Subgroups of Intrahepatic Cholangiocarcinoma Discovered by Single-Cell RNA Sequencing–Assisted Multiomics Analysis
Supplementary Figure 1 from Autoantibodies Drive Heart Damage Caused by Concomitant Radiation and PD-1 Blockade
Authors: Yan Bo , Hooper D. Craig , Yuan Zhiyong , Wang Changli , Chen Yulong , Lu Bo
Published: April 2023

Supplementary Figure 1
Supplementary Figures from Combination IFNβ and Membrane-Stable CD40L Maximize Tumor Dendritic Cell Activation and Lymph Node Trafficking to Elicit Systemic T-cell Immunity
Authors: Zheng Hong , Yu Xiaoqing , Ibrahim Mohammed L. , Foresman Dana , Xie Mengyu , Johnson Joseph O. , Boyle Theresa A. , Ruffell Brian , Perez Bradford A. , Antonia Scott J. , Ready Neal , Saltos Andreas N. , Cantwell Mark J. , Beg Amer A.
Published: April 2023

Supplementary Figures 1-14