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Intratumoral CD4+ T Cells Mediate Anti-tumor Cytotoxicity in Human Bladder Cancer.
Oh, David Y; Kwek, Serena S; Raju, Siddharth S; Li, Tony; McCarthy, Elizabeth; Chow, Eric; Aran, Dvir; Ilano, Arielle; Pai, Chien-Chun Steven; Rancan, Chiara; Allaire, Kathryn; Burra, Arun; Sun, Yang; Spitzer, Matthew H; Mangul, Serghei; Porten, Sima; Meng, Maxwell V; Friedlander, Terence W; Ye, Chun Jimmie; Fong, Lawrence.
Affiliation
  • Oh DY; Division of Hematology/Oncology, Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
  • Kwek SS; Division of Hematology/Oncology, Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
  • Raju SS; Division of Rheumatology, Department of Medicine; Department of Epidemiology and Biostatistics; and Institute for Human Genetics, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Microbiology and Immunology, University of California, San Francisco, San Francisco,
  • Li T; Division of Hematology/Oncology, Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
  • McCarthy E; Division of Rheumatology, Department of Medicine; Department of Epidemiology and Biostatistics; and Institute for Human Genetics, University of California, San Francisco, San Francisco, CA 94143, USA.
  • Chow E; Department of Biochemistry and Biophysics, Center for Advanced Technologies, University of California, San Francisco, San Francisco, CA 94143, USA.
  • Aran D; Bakar Computational Health Sciences Institute, University of California, San Francisco, San Francisco, CA 94143, USA.
  • Ilano A; Division of Hematology/Oncology, Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
  • Pai CS; Division of Hematology/Oncology, Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
  • Rancan C; Division of Hematology/Oncology, Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
  • Allaire K; Division of Hematology/Oncology, Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
  • Burra A; Division of Hematology/Oncology, Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
  • Sun Y; Division of Rheumatology, Department of Medicine; Department of Epidemiology and Biostatistics; and Institute for Human Genetics, University of California, San Francisco, San Francisco, CA 94143, USA.
  • Spitzer MH; Parker Institute for Cancer Immunotherapy, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Otolaryngology - Head and Neck Surgery, University of Cali
  • Mangul S; Department of Computer Science, University of California, Los Angeles, Los Angeles, CA 90095, USA.
  • Porten S; Department of Urology, University of California, San Francisco, San Francisco, CA 94143, USA.
  • Meng MV; Department of Urology, University of California, San Francisco, San Francisco, CA 94143, USA.
  • Friedlander TW; Division of Hematology/Oncology, Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
  • Ye CJ; Parker Institute for Cancer Immunotherapy, University of California, San Francisco, San Francisco, CA 94143, USA; Division of Rheumatology, Department of Medicine; Department of Epidemiology and Biostatistics; and Institute for Human Genetics, University of California, San Francisco, San Francisco,
  • Fong L; Division of Hematology/Oncology, Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA; Parker Institute for Cancer Immunotherapy, University of California, San Francisco, San Francisco, CA 94143, USA. Electronic address: lawrence.fong@ucsf.edu.
Cell ; 181(7): 1612-1625.e13, 2020 06 25.
Article in En | MEDLINE | ID: mdl-32497499
Responses to anti-PD-1 immunotherapy occur but are infrequent in bladder cancer. The specific T cells that mediate tumor rejection are unknown. T cells from human bladder tumors and non-malignant tissue were assessed with single-cell RNA and paired T cell receptor (TCR) sequencing of 30,604 T cells from 7 patients. We find that the states and repertoires of CD8+ T cells are not distinct in tumors compared with non-malignant tissues. In contrast, single-cell analysis of CD4+ T cells demonstrates several tumor-specific states, including multiple distinct states of regulatory T cells. Surprisingly, we also find multiple cytotoxic CD4+ T cell states that are clonally expanded. These CD4+ T cells can kill autologous tumors in an MHC class II-dependent fashion and are suppressed by regulatory T cells. Further, a gene signature of cytotoxic CD4+ T cells in tumors predicts a clinical response in 244 metastatic bladder cancer patients treated with anti-PD-L1.
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Full text: 1 Database: MEDLINE Main subject: Urinary Bladder Neoplasms / CD4-Positive T-Lymphocytes Limits: Humans Language: En Journal: Cell Year: 2020 Type: Article Affiliation country: United States
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Full text: 1 Database: MEDLINE Main subject: Urinary Bladder Neoplasms / CD4-Positive T-Lymphocytes Limits: Humans Language: En Journal: Cell Year: 2020 Type: Article Affiliation country: United States