Cancer CellPub Date : 2025-01-16DOI: 10.1016/j.ccell.2024.12.009
Kevin M. Boehm, Francisco Sánchez-Vega
{"title":"Simplifying clinical use of TCGA molecular subtypes through machine learning models","authors":"Kevin M. Boehm, Francisco Sánchez-Vega","doi":"10.1016/j.ccell.2024.12.009","DOIUrl":"https://doi.org/10.1016/j.ccell.2024.12.009","url":null,"abstract":"In this issue of <em>Cancer Cell,</em> Ellrott et al. present machine learning models to classify samples into The Cancer Genome Atlas molecular subtypes using compact sets of genomic features. These validated, ready-to-use models are publicly available, although some clinical hurdles need to be cleared before they are fully implemented.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"28 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142987027","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cancer CellPub Date : 2025-01-16DOI: 10.1016/j.ccell.2024.12.008
Amelia Acha-Sagredo, Pietro Andrei, Kalum Clayton, Emma Taggart, Carlotta Antoniotti, Chloé A. Woodman, Hassnae Afrache, Constance Fourny, Maria Armero, Hafsa Kaja Moinudeen, Mary Green, Nisha Bhardwaj, Anna Mikolajczak, Maria Rodriguez-Lopez, Marg Crawford, Emma Connick, Steven Lim, Philip Hobson, Josep Linares, Ekaterina Ignatova, Francesca D. Ciccarelli
{"title":"A constitutive interferon-high immunophenotype defines response to immunotherapy in colorectal cancer","authors":"Amelia Acha-Sagredo, Pietro Andrei, Kalum Clayton, Emma Taggart, Carlotta Antoniotti, Chloé A. Woodman, Hassnae Afrache, Constance Fourny, Maria Armero, Hafsa Kaja Moinudeen, Mary Green, Nisha Bhardwaj, Anna Mikolajczak, Maria Rodriguez-Lopez, Marg Crawford, Emma Connick, Steven Lim, Philip Hobson, Josep Linares, Ekaterina Ignatova, Francesca D. Ciccarelli","doi":"10.1016/j.ccell.2024.12.008","DOIUrl":"https://doi.org/10.1016/j.ccell.2024.12.008","url":null,"abstract":"Fewer than 50% of metastatic deficient mismatch repair (dMMR) colorectal cancer (CRC) patients respond to immune checkpoint inhibition (ICI). Identifying and expanding this patient population remains a pressing clinical need. Here, we report that an interferon-high immunophenotype locally enriched in cytotoxic lymphocytes and antigen-presenting macrophages is required for response. This immunophenotype is not exclusive to dMMR CRCs but comprises a subset of MMR proficient (pMMR) CRCs. Single-cell spatial analysis and <em>in vitro</em> cell co-cultures indicate that interferon-producing cytotoxic T cells induce overexpression of antigen presentation in adjacent macrophages and tumor cells, including MHC class II invariant chain <em>CD74</em>. dMMR CRCs expressing high levels of CD74 respond to ICI and a subset of CD74 high pMMR CRC patients show better progression free survival when treated with ICI. Therefore, CD74 abundance can identify the constitutive interferon-high immunophenotype determining clinical benefit in CRC, independently of tumor mutational burden or MMR status.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"119 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142987028","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cancer CellPub Date : 2025-01-02DOI: 10.1016/j.ccell.2024.12.007
Elijah Kirschstein, Andrew J. Gunderson
{"title":"Plasma cell and cancer stem cell crosstalk in glioblastoma","authors":"Elijah Kirschstein, Andrew J. Gunderson","doi":"10.1016/j.ccell.2024.12.007","DOIUrl":"https://doi.org/10.1016/j.ccell.2024.12.007","url":null,"abstract":"Plasma cells (PCs) are the main producers of antibodies and have context-dependent roles in tumor immunity. In this issue of <em>Cancer Cell</em>, Gao et al. report that intratumoral PCs drive maintenance of glioblastoma stem cells to promote tumor growth via IgG secretion that activates a FcγRIIA-SYK-AKT signaling axis.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"4 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142912151","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Infiltrating plasma cells maintain glioblastoma stem cells through IgG-Tumor binding","authors":"Jiancheng Gao, Danling Gu, Kailin Yang, Junxia Zhang, Qiankun Lin, Wei Yuan, Xu Zhu, Deobrat Dixit, Ryan C. Gimple, Hao You, Qian Zhang, Zhumei Shi, Xiao Fan, Qiulian Wu, Chenfei Lu, Zhangchun Cheng, Daqi Li, Linjie Zhao, Bin Xue, Zhu Zhu, Xiuxing Wang","doi":"10.1016/j.ccell.2024.12.006","DOIUrl":"https://doi.org/10.1016/j.ccell.2024.12.006","url":null,"abstract":"Glioblastoma is a highly aggressive primary brain tumor with glioblastoma stem cells (GSCs) enforcing the intra-tumoral hierarchy. Plasma cells (PCs) are critical effectors of the B-lineage immune system, but their roles in glioblastoma remain largely unexplored. Here, we leverage single-cell RNA and B cell receptor sequencing of tumor-infiltrating B-lineage cells and reveal that PCs are aberrantly enriched in the glioblastoma-infiltrating B-lineage population, experience low level of somatic hypermutation, and are associated with poor prognosis. PCs secrete immunoglobulin G (IgG), which stimulates GSC proliferation via the IgG-FcγRIIA-AKT-mTOR axis. Disruption of IgG-FcγRIIA paracrine communication inhibits GSC proliferation and self-renewal. Glioblastoma-infiltrating PCs are recruited to GSC niches via CCL2-CCR2 chemokine program. GSCs further derive pro-proliferative signals from broadly utilized monoclonal antibody-based immune checkpoint inhibitors via FcγRIIA signaling. Our data generate an atlas of B-lineage cells in glioblastoma with a framework for combinatorial targeting of both tumor cell-intrinsic and microenvironmental dependencies.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"5 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142912023","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cancer CellPub Date : 2025-01-02DOI: 10.1016/j.ccell.2024.12.002
Kyle Ellrott, Christopher K. Wong, Christina Yau, Mauro A.A. Castro, Jordan A. Lee, Brian J. Karlberg, Jasleen K. Grewal, Vincenzo Lagani, Bahar Tercan, Verena Friedl, Toshinori Hinoue, Vladislav Uzunangelov, Lindsay Westlake, Xavier Loinaz, Ina Felau, Peggy I. Wang, Anab Kemal, Samantha J. Caesar-Johnson, Ilya Shmulevich, Alexander J. Lazar, Peter W. Laird
{"title":"Classification of non-TCGA cancer samples to TCGA molecular subtypes using compact feature sets","authors":"Kyle Ellrott, Christopher K. Wong, Christina Yau, Mauro A.A. Castro, Jordan A. Lee, Brian J. Karlberg, Jasleen K. Grewal, Vincenzo Lagani, Bahar Tercan, Verena Friedl, Toshinori Hinoue, Vladislav Uzunangelov, Lindsay Westlake, Xavier Loinaz, Ina Felau, Peggy I. Wang, Anab Kemal, Samantha J. Caesar-Johnson, Ilya Shmulevich, Alexander J. Lazar, Peter W. Laird","doi":"10.1016/j.ccell.2024.12.002","DOIUrl":"https://doi.org/10.1016/j.ccell.2024.12.002","url":null,"abstract":"Molecular subtypes, such as defined by The Cancer Genome Atlas (TCGA), delineate a cancer’s underlying biology, bringing hope to inform a patient’s prognosis and treatment plan. However, most approaches used in the discovery of subtypes are not suitable for assigning subtype labels to new cancer specimens from other studies or clinical trials. Here, we address this barrier by applying five different machine learning approaches to multi-omic data from 8,791 TCGA tumor samples comprising 106 subtypes from 26 different cancer cohorts to build models based upon small numbers of features that can classify new samples into previously defined TCGA molecular subtypes—a step toward molecular subtype application in the clinic. We validate select classifiers using external datasets. Predictive performance and classifier-selected features yield insight into the different machine-learning approaches and genomic data platforms. For each cancer and data type we provide containerized versions of the top-performing models as a public resource.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"92 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142912148","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cancer CellPub Date : 2025-01-02DOI: 10.1016/j.ccell.2024.12.004
WonJae Lee, Song Yi Ko, Hironari Akasaka, Melanie Weigert, Ernst Lengyel, Honami Naora
{"title":"Neutrophil extracellular traps promote pre-metastatic niche formation in the omentum by expanding innate-like B cells that express IL-10","authors":"WonJae Lee, Song Yi Ko, Hironari Akasaka, Melanie Weigert, Ernst Lengyel, Honami Naora","doi":"10.1016/j.ccell.2024.12.004","DOIUrl":"https://doi.org/10.1016/j.ccell.2024.12.004","url":null,"abstract":"Disseminated cancer cells in the peritoneal fluid often colonize omental fat-associated lymphoid clusters but the mechanisms are unclear. Here, we identify that innate-like B cells accumulate in the omentum of mice and women with early-stage ovarian cancer concomitantly with the extrusion of chromatin fibers by neutrophils called neutrophil extracellular traps (NETs). Studies using genetically modified NET-deficient mice, pharmacologic inhibition of NETs, and adoptive B cell transfer show that NETs induce expression of the chemoattractant CXCL13 in the pre-metastatic omentum, stimulating recruitment of peritoneal innate-like B cells that in turn promote expansion of regulatory T cells and omental metastasis through producing interleukin (IL)-10. <em>Ex vivo</em> studies show that NETs elicit IL-10 production in innate-like B cells by inactivating SHP-1, a phosphatase that inhibits B cell activation pathways, and by generating reactive oxygen species. These findings reveal that NETs alter immune cell dynamics in the pre-metastatic omentum, rendering this niche conducive for colonization.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"74 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142912149","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cancer CellPub Date : 2025-01-02DOI: 10.1016/j.ccell.2024.12.005
Marta Lebrusant-Fernandez, James L. Reading
{"title":"Beta papillomaviruses: From foe to friend in skin cancer immunity","authors":"Marta Lebrusant-Fernandez, James L. Reading","doi":"10.1016/j.ccell.2024.12.005","DOIUrl":"https://doi.org/10.1016/j.ccell.2024.12.005","url":null,"abstract":"In this issue of <em>Cancer Cell</em>, Son et al. highlight an unexpected role for skin β-papillomaviruses in the protection against skin carcinogenesis. T cell immunity to skin papillomaviruses blocks the expansion of p53 mutant clones in ultraviolet (UV) radiation-damaged skin, preventing the development of skin cancer.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"22 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142912147","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Targeting P4HA1 promotes CD8+ T cell progenitor expansion toward immune memory and systemic anti-tumor immunity","authors":"Shijun Ma, Li-Teng Ong, Zemin Jiang, Wee Chyan Lee, Puay Leng Lee, Mubaraka Yusuf, Henrik J. Ditzel, Yulan Wang, Qingfeng Chen, Wenyu Wang, Xiaojian Wu, Ern Yu Tan, Qiang Yu","doi":"10.1016/j.ccell.2024.12.001","DOIUrl":"https://doi.org/10.1016/j.ccell.2024.12.001","url":null,"abstract":"Successful immunotherapy relies on both intratumoral and systemic immunity, which is yet to be achieved for most patients with cancer. Here, we identify <em>P4HA1</em>, encoding prolyl 4-hydroxylase 1, as a crucial regulator of CD8<sup>+</sup> T cell differentiation strongly upregulated in tumor-draining lymph nodes (TDLNs) and hypoxic tumor microenvironment. P4HA1 accumulates in mitochondria, disrupting the tricarboxylic acid (TCA) cycle through aberrant α-ketoglutarate and succinate metabolism, promoting mitochondria unfitness and exhaustion while suppressing progenitor expansion. Targeting P4HA1 enhances both adoptive and endogenous TCF1<sup>+</sup> CD8<sup>+</sup> T progenitor expansion while mitigating the development of exhaustion in the tumor, TDLN, and blood, enabling a notable and durable systemic anti-cancer immunity. We propose that P4HA1 induction in CD8<sup>+</sup> T cells in cancer orchestrates an immune-escape program, offering a T cell-directed target for system immunotherapy in solid tumors.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"33 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142886804","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cancer CellPub Date : 2024-12-12DOI: 10.1016/j.ccell.2024.11.011
Courtney T. Kureshi, Stephanie K. Dougan
{"title":"Cytokines in cancer","authors":"Courtney T. Kureshi, Stephanie K. Dougan","doi":"10.1016/j.ccell.2024.11.011","DOIUrl":"https://doi.org/10.1016/j.ccell.2024.11.011","url":null,"abstract":"Cytokines are proteins used by immune cells to communicate with each other and with cells in their environment. The pleiotropic effects of cytokine networks are determined by which cells express cytokines and which cells express cytokine receptors, with downstream outcomes that can differ based on cell type and environmental cues. Certain cytokines, such as interferon (IFN)-γ, have been clearly linked to anti-tumor immunity, while others, such as the innate inflammatory cytokines, promote oncogenesis. Here we provide an overview of the functional roles of cytokines in the tumor microenvironment. Although we have a sophisticated understanding of cytokine networks, therapeutically targeting cytokine pathways in cancer has been challenging. We discuss current progress in cytokine blockade, cytokine-based therapies, and engineered cytokine therapeutics as emerging cancer treatments of interest.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"4 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142809963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cancer CellPub Date : 2024-12-12DOI: 10.1016/j.ccell.2024.11.008
Zhen Yang, Xinpeng Liu, Jun Zhu, Yangyang Chai, Boyi Cong, Bo Li, Wanfeng Gao, Ye Hu, Mingyue Wen, Yanfang Liu, Li Fu, Xuetao Cao
{"title":"Inhibiting intracellular CD28 in cancer cells enhances antitumor immunity and overcomes anti-PD-1 resistance via targeting PD-L1","authors":"Zhen Yang, Xinpeng Liu, Jun Zhu, Yangyang Chai, Boyi Cong, Bo Li, Wanfeng Gao, Ye Hu, Mingyue Wen, Yanfang Liu, Li Fu, Xuetao Cao","doi":"10.1016/j.ccell.2024.11.008","DOIUrl":"https://doi.org/10.1016/j.ccell.2024.11.008","url":null,"abstract":"Deciphering mechanisms for cancer immune escape may provide targets for improving immunotherapy efficacy. By <em>in vivo</em> genome-wide CRISPR loss-of-function screening in a mouse model of triple negative breast cancer (TNBC), we uncovered a non-classical function of <em>Cd28</em> in cancer cells to promote immune escape. Knocking out <em>Cd28</em> in cancer cells increased infiltration of type I conventional DC (cDC1) and activated tumor-specific CD8<sup>+</sup> T cells, and pharmaceutical inducible knockdown of <em>Cd28</em> inhibited pre-established tumor growth and overcame anti-PD-1 resistance <em>in vivo</em>. Furthermore, high expression of cancer cell CD28 in human TNBC tissues correlated with elevated PD-L1 expression, less CD8<sup>+</sup> T cell infiltration, and poor prognosis. Mechanistically, intracellular CD28 directly bound to <em>Cd274</em> mRNA and recruited spliceosomal factor SNRPB2 to stabilize <em>Cd274</em> mRNA in nucleus, promoting PD-L1 expression and immune escape. Therefore, disrupting cancer cell CD28-mediated immune escape may provide a potential approach to improve breast cancer immunotherapy.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"22 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142809464","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}