Pub Date : 2025-02-06DOI: 10.1016/j.ccell.2025.01.008
Francisco Javier Rodriguez-Baena, Angel Marquez-Galera, Pablo Ballesteros-Martinez, Alba Castillo, Eva Diaz, Gema Moreno-Bueno, Jose P. Lopez-Atalaya, Berta Sanchez-Laorden
Melanoma is one of the tumor types with the highest risk of brain metastasis. However, the biology of melanoma brain metastasis and the role of the brain immune microenvironment in treatment responses are not yet fully understood. Using preclinical models and single-cell transcriptomics, we have identified a mechanism that enhances antitumor immunity in melanoma brain metastasis. We show that activation of the Rela/Nuclear Factor κB (NF-κB) pathway in microglia promotes melanoma brain metastasis. Targeting this pathway elicits microglia reprogramming toward a proinflammatory phenotype, which enhances antitumor immunity and reduces brain metastatic burden. Furthermore, we found that proinflammatory microglial markers in melanoma brain metastasis are associated with improved responses to immune checkpoint inhibitors in patients and targeting Rela/NF-κB pathway in mice improves responses to these therapies in the brain, suggesting a strategy to enhance antitumor immunity and responses to immune checkpoint inhibitors in patients with melanoma brain metastasis.
{"title":"Microglial reprogramming enhances antitumor immunity and immunotherapy response in melanoma brain metastases","authors":"Francisco Javier Rodriguez-Baena, Angel Marquez-Galera, Pablo Ballesteros-Martinez, Alba Castillo, Eva Diaz, Gema Moreno-Bueno, Jose P. Lopez-Atalaya, Berta Sanchez-Laorden","doi":"10.1016/j.ccell.2025.01.008","DOIUrl":"https://doi.org/10.1016/j.ccell.2025.01.008","url":null,"abstract":"Melanoma is one of the tumor types with the highest risk of brain metastasis. However, the biology of melanoma brain metastasis and the role of the brain immune microenvironment in treatment responses are not yet fully understood. Using preclinical models and single-cell transcriptomics, we have identified a mechanism that enhances antitumor immunity in melanoma brain metastasis. We show that activation of the Rela/Nuclear Factor κB (NF-κB) pathway in microglia promotes melanoma brain metastasis. Targeting this pathway elicits microglia reprogramming toward a proinflammatory phenotype, which enhances antitumor immunity and reduces brain metastatic burden. Furthermore, we found that proinflammatory microglial markers in melanoma brain metastasis are associated with improved responses to immune checkpoint inhibitors in patients and targeting Rela/NF-κB pathway in mice improves responses to these therapies in the brain, suggesting a strategy to enhance antitumor immunity and responses to immune checkpoint inhibitors in patients with melanoma brain metastasis.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"228 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143192536","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}
Pub Date : 2025-01-30DOI: 10.1016/j.ccell.2025.01.001
Xinyi Guo, Hu Nie, Wenwen Zhang, Jiesheng Li, Jing Ge, Bowen Xie, Wenbo Hu, Yicheng Zhu, Na Zhong, Xinmei Zhang, Xiaohong Zhao, Xiaoshuang Wang, Qinli Sun, Kun Wei, Xiaoyuan Chen, Ling Ni, Ting Zhang, Shichun Lu, Lei Zhang, Chen Dong
Combination of anti-PD-1 with lenvatinib showed clinical efficacy in multiple cancers, yet the underlying immunological mechanisms are unclear. Here, we compared T cells in hepatocellular carcinoma (HCC) patients before and after combination treatment using single-cell transcriptomics and T cell receptor (scTCR) clonotype analyses. We found that tumor-infiltrating GZMK+ CD8+ effector/effector memory T (Teff/Tem) cells, showing a favorable response to combination therapy, comprise progenitor exhausted T (Tpex) cells and also unappreciated circulating Tem (cTem) cells enriched with hepatitis B virus (HBV) specificity. Further integrated analyses revealed that cTem cells are specifically associated with responsiveness to the combination therapy, whereas Tpex cells contribute to responses in both combination therapy and anti-PD-1 monotherapy. Notably, an underexplored KIR+ CD8+ T cell subset in the tumor and FOXP3+ CD4+ regulatory T cells are specifically enriched in non-responders after the combination therapy. Our study thus elucidated T cell subsets associated with clinical benefits and resistance in cancer immunotherapy.
{"title":"Contrasting cytotoxic and regulatory T cell responses underlying distinct clinical outcomes to anti-PD-1 plus lenvatinib therapy in cancer","authors":"Xinyi Guo, Hu Nie, Wenwen Zhang, Jiesheng Li, Jing Ge, Bowen Xie, Wenbo Hu, Yicheng Zhu, Na Zhong, Xinmei Zhang, Xiaohong Zhao, Xiaoshuang Wang, Qinli Sun, Kun Wei, Xiaoyuan Chen, Ling Ni, Ting Zhang, Shichun Lu, Lei Zhang, Chen Dong","doi":"10.1016/j.ccell.2025.01.001","DOIUrl":"https://doi.org/10.1016/j.ccell.2025.01.001","url":null,"abstract":"Combination of anti-PD-1 with lenvatinib showed clinical efficacy in multiple cancers, yet the underlying immunological mechanisms are unclear. Here, we compared T cells in hepatocellular carcinoma (HCC) patients before and after combination treatment using single-cell transcriptomics and T cell receptor (scTCR) clonotype analyses. We found that tumor-infiltrating <em>GZMK</em><sup>+</sup> CD8<sup>+</sup> effector/effector memory T (Teff/Tem) cells, showing a favorable response to combination therapy, comprise progenitor exhausted T (Tpex) cells and also unappreciated circulating Tem (cTem) cells enriched with hepatitis B virus (HBV) specificity. Further integrated analyses revealed that cTem cells are specifically associated with responsiveness to the combination therapy, whereas Tpex cells contribute to responses in both combination therapy and anti-PD-1 monotherapy. Notably, an underexplored <em>KIR</em><sup>+</sup> CD8<sup>+</sup> T cell subset in the tumor and <em>FOXP3</em><sup>+</sup> CD4<sup>+</sup> regulatory T cells are specifically enriched in non-responders after the combination therapy. Our study thus elucidated T cell subsets associated with clinical benefits and resistance in cancer immunotherapy.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"74 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143056430","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}
Pub Date : 2025-01-30DOI: 10.1016/j.ccell.2024.12.003
Peter J. Matulich, Megan L. Burger
The mechanisms underlying synergy between checkpoint blockade and anti-angiogenic therapy remain elusive. In this issue of Cancer Cell, Guo et al. analyze hepatocellular carcinoma patients treated with anti-PD-1 and lenvatinib, identifying a circulating CD8+ T cell population critical for treatment efficacy. Engaging these cells could enhance immunotherapy across other settings.
{"title":"Circulating T cells fuel anti-PD-1 and lenvatinib efficacy","authors":"Peter J. Matulich, Megan L. Burger","doi":"10.1016/j.ccell.2024.12.003","DOIUrl":"https://doi.org/10.1016/j.ccell.2024.12.003","url":null,"abstract":"The mechanisms underlying synergy between checkpoint blockade and anti-angiogenic therapy remain elusive. In this issue of <em>Cancer Cell</em>, Guo et al. analyze hepatocellular carcinoma patients treated with anti-PD-1 and lenvatinib, identifying a circulating CD8<sup>+</sup> T cell population critical for treatment efficacy. Engaging these cells could enhance immunotherapy across other settings.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"27 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143057038","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}
Pub Date : 2025-01-16DOI: 10.1016/j.ccell.2024.12.009
Kevin M. Boehm, Francisco Sánchez-Vega
In this issue of Cancer Cell, 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.
在这一期的《癌症细胞》中，Ellrott等人提出了机器学习模型，利用紧凑的基因组特征集将样本分类为The Cancer Genome Atlas分子亚型。这些经过验证的可随时使用的模型是公开的，尽管在完全实施之前需要清除一些临床障碍。
{"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}
Pub 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
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 in vitro 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 CD74. 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.
{"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}
Pub Date : 2025-01-02DOI: 10.1016/j.ccell.2024.12.007
Elijah Kirschstein, Andrew J. Gunderson
Plasma cells (PCs) are the main producers of antibodies and have context-dependent roles in tumor immunity. In this issue of Cancer Cell, 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.
浆细胞（PCs）是抗体的主要产生者，在肿瘤免疫中具有环境依赖性作用。在这一期的Cancer Cell中，Gao等报道了肿瘤内的pc通过激活fc - γ riia - syk - akt信号轴的IgG分泌来驱动胶质母细胞瘤干细胞的维持，从而促进肿瘤的生长。
{"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}
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.
胶质母细胞瘤是一种高度侵袭性的原发性脑肿瘤，胶质母细胞瘤干细胞（GSCs）加强了肿瘤内的等级。浆细胞（PCs）是b系免疫系统的关键效应器，但它们在胶质母细胞瘤中的作用仍未得到充分研究。在这里，我们利用肿瘤浸润B系细胞的单细胞RNA和B细胞受体测序，揭示了pc在胶质母细胞瘤浸润B系人群中异常富集，经历低水平的体细胞超突变，并与不良预后相关。PCs分泌免疫球蛋白G (IgG)，通过IgG- fc - γ riia - akt - mtor轴刺激GSC增殖。破坏igg - fc - γ - riia旁分泌通讯抑制GSC增殖和自我更新。胶质母细胞瘤浸润性pc通过CCL2-CCR2趋化因子程序被招募到GSC壁龛。GSCs进一步通过FcγRIIA信号从广泛使用的基于单克隆抗体的免疫检查点抑制剂中获得促增殖信号。我们的数据生成了胶质母细胞瘤中b系细胞的图谱，该图谱具有肿瘤细胞内在和微环境依赖性的组合靶向框架。
{"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}
Pub Date : 2025-01-02DOI: 10.1016/j.ccell.2024.12.004
WonJae Lee, Song Yi Ko, Hironari Akasaka, Melanie Weigert, Ernst Lengyel, Honami Naora
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. Ex vivo 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.
{"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}
Pub 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
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.
{"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}
Pub Date : 2025-01-02DOI: 10.1016/j.ccell.2024.12.005
Marta Lebrusant-Fernandez, James L. Reading
In this issue of Cancer Cell, 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.
{"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}
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