Cancer Cell最新文献

Cytokines in cancer

IF 50.3 1区医学

Cancer Cell Pub Date : 2024-12-12 DOI: 10.1016/j.ccell.2024.11.011

Courtney T. Kureshi, Stephanie K. Dougan

引用次数: 0

Inhibiting intracellular CD28 in cancer cells enhances antitumor immunity and overcomes anti-PD-1 resistance via targeting PD-L1

IF 50.3 1区医学

Cancer Cell Pub Date : 2024-12-12 DOI: 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 in vivo genome-wide CRISPR loss-of-function screening in a mouse model of triple negative breast cancer (TNBC), we uncovered a non-classical function of Cd28 in cancer cells to promote immune escape. Knocking out Cd28 in cancer cells increased infiltration of type I conventional DC (cDC1) and activated tumor-specific CD8+ T cells, and pharmaceutical inducible knockdown of Cd28 inhibited pre-established tumor growth and overcame anti-PD-1 resistance in vivo. Furthermore, high expression of cancer cell CD28 in human TNBC tissues correlated with elevated PD-L1 expression, less CD8+ T cell infiltration, and poor prognosis. Mechanistically, intracellular CD28 directly bound to Cd274 mRNA and recruited spliceosomal factor SNRPB2 to stabilize Cd274 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}

引用次数: 0

Breaking the mold: Unconventional T cells in cancer therapy

IF 50.3 1区医学

Cancer Cell Pub Date : 2024-12-12 DOI: 10.1016/j.ccell.2024.11.010

Yan-Ruide Li, Kuangyi Zhou, Yichen Zhu, Tyler Halladay, Lili Yang

引用次数: 0

A metabolic pathway for improving adoptive cellular therapy

IF 50.3 1区医学

Cancer Cell Pub Date : 2024-12-12 DOI: 10.1016/j.ccell.2024.11.014

Christina M. Scheffler, Paul A. Beavis, Phillip K. Darcy

引用次数: 0

Daily glucocorticoids promote glioblastoma growth and circadian synchrony to the host

IF 50.3 1区医学

Cancer Cell Pub Date : 2024-12-12 DOI: 10.1016/j.ccell.2024.11.012

Maria F. Gonzalez-Aponte, Anna R. Damato, Tatiana Simon, Nigina Aripova, Fabrizio Darby, Myung Sik Jeon, Jingqin Luo, Joshua B. Rubin, Erik D. Herzog

{"title":"Daily glucocorticoids promote glioblastoma growth and circadian synchrony to the host","authors":"Maria F. Gonzalez-Aponte, Anna R. Damato, Tatiana Simon, Nigina Aripova, Fabrizio Darby, Myung Sik Jeon, Jingqin Luo, Joshua B. Rubin, Erik D. Herzog","doi":"10.1016/j.ccell.2024.11.012","DOIUrl":"https://doi.org/10.1016/j.ccell.2024.11.012","url":null,"abstract":"Glioblastoma (GBM) is the most common primary malignant brain tumor in adults with a poor prognosis despite aggressive therapy. Here, we hypothesized that daily host signaling regulates tumor growth and synchronizes circadian rhythms in GBM. We find daily glucocorticoids promote or suppress GBM growth through glucocorticoid receptor (GR) signaling depending on time of day and the clock genes, Bmal1 and Cry. Blocking circadian signals, like vasoactive intestinal peptide or glucocorticoids, dramatically slows GBM growth and disease progression. Analysis of human GBM samples from The Cancer Genome Atlas (TCGA) shows that high GR expression significantly increases hazard of mortality. Finally, mouse and human GBM models have intrinsic circadian rhythms in clock gene expression in vitro and in vivo that entrain to the host through glucocorticoid signaling, regardless of tumor type or host immune status. We conclude that GBM entrains to the circadian circuit of the brain, modulating its growth through clock-controlled cues, like glucocorticoids.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"24 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142809462","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

Advances in liquid biopsy: From exploration to practical application

IF 50.3 1区医学

Cancer Cell Pub Date : 2024-12-12 DOI: 10.1016/j.ccell.2024.11.009

Catherine Alix-Panabières, Klaus Pantel

引用次数: 0

Stressing the importance of circadian time in treatment responses

IF 50.3 1区医学

Cancer Cell Pub Date : 2024-12-12 DOI: 10.1016/j.ccell.2024.11.004

Katja A. Lamia

引用次数: 0

Commensal papillomavirus immunity preserves the homeostasis of highly mutated normal skin

IF 50.3 1区医学

Cancer Cell Pub Date : 2024-12-12 DOI: 10.1016/j.ccell.2024.11.013

Heehwa G. Son, Dat Thinh Ha, Yun Xia, Tiancheng Li, Jasmine Blandin, Tomonori Oka, Marjan Azin, Danielle N. Conrad, Can Zhou, Yuhan Zeng, Tatsuya Hasegawa, John D. Strickley, Jonathan L. Messerschmidt, Ranya Guennoun, Tal H. Erlich, Gregory L. Shoemaker, Luke H. Johnson, Kenneth E. Palmer, David E. Fisher, Thomas D. Horn, Shadmehr Demehri

{"title":"Commensal papillomavirus immunity preserves the homeostasis of highly mutated normal skin","authors":"Heehwa G. Son, Dat Thinh Ha, Yun Xia, Tiancheng Li, Jasmine Blandin, Tomonori Oka, Marjan Azin, Danielle N. Conrad, Can Zhou, Yuhan Zeng, Tatsuya Hasegawa, John D. Strickley, Jonathan L. Messerschmidt, Ranya Guennoun, Tal H. Erlich, Gregory L. Shoemaker, Luke H. Johnson, Kenneth E. Palmer, David E. Fisher, Thomas D. Horn, Shadmehr Demehri","doi":"10.1016/j.ccell.2024.11.013","DOIUrl":"https://doi.org/10.1016/j.ccell.2024.11.013","url":null,"abstract":"Immunosuppression commonly disrupts the homeostasis of mutated normal skin, leading to widespread skin dysplasia and field cancerization. However, the immune system’s role in maintaining the normal state of mutated tissues remains uncertain. Herein, we demonstrate that T cell immunity to cutaneotropic papillomaviruses promotes the homeostasis of ultraviolet radiation-damaged skin. Mouse papillomavirus (MmuPV1) colonization blocks the expansion of mutant p53 clones in the epidermis in a CD8+ T cell-dependent manner. MmuPV1 activity is increased in p53-deficient keratinocytes, leading to their specific targeting by CD8+ T cells in the skin. Sun-exposed human skin containing mutant p53 clones shows increased epidermal beta-human papillomavirus (β-HPV) activity and CD8+ T cell infiltrates compared with sun-protected skin. The expansion of mutant p53 clones in premalignant skin lesions associates with β-HPV loss. Thus, immunity to commensal HPVs contributes to the homeostasis of mutated normal skin, highlighting the role of virome-immune system interactions in preserving aging human tissues.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"58 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142809463","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

Chemotherapy induces myeloid-driven spatially confined T cell exhaustion in ovarian cancer

IF 50.3 1区医学

Cancer Cell Pub Date : 2024-12-09 DOI: 10.1016/j.ccell.2024.11.005

Inga-Maria Launonen, Iga Niemiec, María Hincapié-Otero, Erdogan Pekcan Erkan, Ada Junquera, Daria Afenteva, Matias M. Falco, Zhihan Liang, Matilda Salko, Foteini Chamchougia, Angela Szabo, Fernando Perez-Villatoro, Yilin Li, Giulia Micoli, Ashwini Nagaraj, Ulla-Maija Haltia, Essi Kahelin, Jaana Oikkonen, Johanna Hynninen, Anni Virtanen, Anniina Färkkilä

{"title":"Chemotherapy induces myeloid-driven spatially confined T cell exhaustion in ovarian cancer","authors":"Inga-Maria Launonen, Iga Niemiec, María Hincapié-Otero, Erdogan Pekcan Erkan, Ada Junquera, Daria Afenteva, Matias M. Falco, Zhihan Liang, Matilda Salko, Foteini Chamchougia, Angela Szabo, Fernando Perez-Villatoro, Yilin Li, Giulia Micoli, Ashwini Nagaraj, Ulla-Maija Haltia, Essi Kahelin, Jaana Oikkonen, Johanna Hynninen, Anni Virtanen, Anniina Färkkilä","doi":"10.1016/j.ccell.2024.11.005","DOIUrl":"https://doi.org/10.1016/j.ccell.2024.11.005","url":null,"abstract":"Anti-tumor immunity is crucial for high-grade serous ovarian cancer (HGSC) prognosis, yet its adaptation upon standard chemotherapy remains poorly understood. Here, we conduct spatial and molecular characterization of 117 HGSC samples collected before and after chemotherapy. Our single-cell and spatial analyses reveal increasingly versatile immune cell states forming spatiotemporally dynamic microcommunities. We describe Myelonets, networks of interconnected myeloid cells that contribute to CD8+ T cell exhaustion post-chemotherapy and show that M1/M2 polarization at the tumor-stroma interface is associated with CD8+ T cell exhaustion and exclusion, correlating with poor chemoresponse. Single-cell and spatial transcriptomics reveal prominent myeloid-T cell interactions via NECTIN2-TIGIT induced by chemotherapy. Targeting these interactions using a functional patient-derived immuno-oncology platform demonstrates that high NECTIN2-TIGIT signaling in matched tumors predicts responses to immune checkpoint blockade. Our discovery of clinically relevant myeloid-driven spatial T cell exhaustion unlocks immunotherapeutic strategies to unleash CD8+ T cell-mediated anti-tumor immunity in HGSC.","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":"95 1","pages":""},"PeriodicalIF":50.3,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142793651","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

Myeloid effector cells in cancer

IF 50.3 1区医学

Cancer Cell Pub Date : 2024-12-09 DOI: 10.1016/j.ccell.2024.11.002

Pieter Schol, Marit J. van Elsas, Jim Middelburg, Maarten K. Nijen Twilhaar, Thorbald van Hall, Tetje C. van der Sluis, Sjoerd H. van der Burg

引用次数: 0