Cancer Cell最新文献_第2页

Multiomic profiling of checkpoint inhibitor-treated melanoma: Identifying predictors of response and resistance, and markers of biological discordance

IF 50.3 1区医学

Cancer Cell Pub Date : 2025-02-06 DOI: 10.1016/j.ccell.2025.01.011

Felicity Newell, Ines Pires da Silva, Peter A. Johansson, Alexander M. Menzies, James S. Wilmott, Venkateswar Addala, Matteo S. Carlino, Helen Rizos, Katia Nones, Jarem J. Edwards, Vanessa Lakis, Stephen H. Kazakoff, Pamela Mukhopadhyay, Peter M. Ferguson, Conrad Leonard, Lambros T. Koufariotis, Scott Wood, Christian U. Blank, John F. Thompson, Andrew J. Spillane, Georgina V. Long

引用次数: 0

Microglial reprogramming enhances antitumor immunity and immunotherapy response in melanoma brain metastases

IF 50.3 1区医学

Cancer Cell Pub Date : 2025-02-06 DOI: 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

{"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}

引用次数: 0

Contrasting cytotoxic and regulatory T cell responses underlying distinct clinical outcomes to anti-PD-1 plus lenvatinib therapy in cancer

IF 50.3 1区医学

Cancer Cell Pub Date : 2025-01-30 DOI: 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

{"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 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.","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}

引用次数: 0

Circulating T cells fuel anti-PD-1 and lenvatinib efficacy

IF 50.3 1区医学

Cancer Cell Pub Date : 2025-01-30 DOI: 10.1016/j.ccell.2024.12.003

Peter J. Matulich, Megan L. Burger

引用次数: 0

Simplifying clinical use of TCGA molecular subtypes through machine learning models 通过机器学习模型简化TCGA分子亚型的临床应用

IF 50.3 1区医学

Cancer Cell Pub Date : 2025-01-16 DOI: 10.1016/j.ccell.2024.12.009

Kevin M. Boehm, Francisco Sánchez-Vega

引用次数: 0

A constitutive interferon-high immunophenotype defines response to immunotherapy in colorectal cancer 组成型干扰素高免疫表型定义了结直肠癌对免疫治疗的反应

IF 50.3 1区医学

Cancer Cell Pub Date : 2025-01-16 DOI: 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 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.","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}

引用次数: 0

Plasma cell and cancer stem cell crosstalk in glioblastoma 胶质母细胞瘤中的浆细胞和肿瘤干细胞串扰

IF 50.3 1区医学

Cancer Cell Pub Date : 2025-01-02 DOI: 10.1016/j.ccell.2024.12.007

Elijah Kirschstein, Andrew J. Gunderson

引用次数: 0

Infiltrating plasma cells maintain glioblastoma stem cells through IgG-Tumor binding 浸润浆细胞通过IgG-Tumor结合维持胶质母细胞瘤干细胞

IF 50.3 1区医学

Cancer Cell Pub Date : 2025-01-02 DOI: 10.1016/j.ccell.2024.12.006

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

{"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}

引用次数: 0

Neutrophil extracellular traps promote pre-metastatic niche formation in the omentum by expanding innate-like B cells that express IL-10 中性粒细胞胞外陷阱通过扩大表达IL-10的先天样B细胞，促进网膜转移前生态位的形成

IF 50.3 1区医学

Cancer Cell Pub Date : 2025-01-02 DOI: 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. 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.","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}

引用次数: 0

Classification of non-TCGA cancer samples to TCGA molecular subtypes using compact feature sets 使用紧凑特征集将非TCGA癌症样本分类为TCGA分子亚型

IF 50.3 1区医学

Cancer Cell Pub Date : 2025-01-02 DOI: 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}

引用次数: 0