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Dynamic CD8+ T cell responses to cancer immunotherapy in human regional lymph nodes are disrupted in metastatic lymph nodes.
Rahim, Maha K; Okholm, Trine Line H; Jones, Kyle B; McCarthy, Elizabeth E; Liu, Candace C; Yee, Jacqueline L; Tamaki, Stanley J; Marquez, Diana M; Tenvooren, Iliana; Wai, Katherine; Cheung, Alexander; Davidson, Brittany R; Johri, Vrinda; Samad, Bushra; O'Gorman, William E; Krummel, Matthew F; van Zante, Annemieke; Combes, Alexis J; Angelo, Michael; Fong, Lawrence; Algazi, Alain P; Ha, Patrick; Spitzer, Matthew H.
Affiliation
  • Rahim MK; Department of Otolaryngology-Head and Neck Surgery, 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; Helen Diller Family Comprehensive Cancer Center, University of
  • Okholm TLH; Department of Otolaryngology-Head and Neck Surgery, 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; Helen Diller Family Comprehensive Cancer Center, University of
  • Jones KB; Department of Otolaryngology-Head and Neck Surgery, 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; Helen Diller Family Comprehensive Cancer Center, University of
  • McCarthy EE; Department of Otolaryngology-Head and Neck Surgery, 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; Helen Diller Family Comprehensive Cancer Center, University of
  • Liu CC; Department of Pathology, Stanford University, Stanford, CA 94304, USA.
  • Yee JL; Department of Otolaryngology-Head and Neck Surgery, 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; Helen Diller Family Comprehensive Cancer Center, University of
  • Tamaki SJ; UCSF CoLabs, University of California, San Francisco, San Francisco, CA 94143, USA.
  • Marquez DM; Department of Otolaryngology-Head and Neck Surgery, 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; Helen Diller Family Comprehensive Cancer Center, University of
  • Tenvooren I; Department of Otolaryngology-Head and Neck Surgery, 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; Helen Diller Family Comprehensive Cancer Center, University of
  • Wai K; Department of Otolaryngology-Head and Neck Surgery, 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; Helen Diller Family Comprehensive Cancer Center, University of
  • Cheung A; Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
  • Davidson BR; UCSF CoLabs, University of California, San Francisco, San Francisco, CA 94143, USA.
  • Johri V; UCSF CoLabs, University of California, San Francisco, San Francisco, CA 94143, USA.
  • Samad B; UCSF CoLabs, University of California, San Francisco, San Francisco, CA 94143, USA.
  • O'Gorman WE; Department of Translational Medicine, Genentech, Inc., South San Francisco, CA 94080, USA.
  • Krummel MF; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Pathology, University of California, San Francisco, San Francisco, CA 94143, USA; Parker Institute for Cancer Immunotherapy, San Francisco, CA 94129, USA.
  • van Zante A; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Pathology, University of California, San Francisco, San Francisco, CA 94143, USA.
  • Combes AJ; UCSF CoLabs, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Pathology, University of California, San Francisco, San Francisco, CA 94143, USA.
  • Angelo M; Department of Pathology, Stanford University, Stanford, CA 94304, USA.
  • Fong L; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA; Parker Institute for Cancer Immunotherapy, San Francisco, CA 94129, USA.
  • Algazi AP; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
  • Ha P; Department of Otolaryngology-Head and Neck Surgery, University of California, San Francisco, San Francisco, CA 94143, USA; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA 94143, USA.
  • Spitzer MH; Department of Otolaryngology-Head and Neck Surgery, 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; Helen Diller Family Comprehensive Cancer Center, University of
Cell ; 186(6): 1127-1143.e18, 2023 03 16.
Article in En | MEDLINE | ID: mdl-36931243
ABSTRACT
CD8+ T cell responses are critical for anti-tumor immunity. While extensively profiled in the tumor microenvironment, recent studies in mice identified responses in lymph nodes (LNs) as essential; however, the role of LNs in human cancer patients remains unknown. We examined CD8+ T cells in human head and neck squamous cell carcinomas, regional LNs, and blood using mass cytometry, single-cell genomics, and multiplexed ion beam imaging. We identified progenitor exhausted CD8+ T cells (Tpex) that were abundant in uninvolved LN and clonally related to terminally exhausted cells in the tumor. After anti-PD-L1 immunotherapy, Tpex in uninvolved LNs reduced in frequency but localized near dendritic cells and proliferating intermediate-exhausted CD8+ T cells (Tex-int), consistent with activation and differentiation. LN responses coincided with increased circulating Tex-int. In metastatic LNs, these response hallmarks were impaired, with immunosuppressive cellular niches. Our results identify important roles for LNs in anti-tumor immune responses in humans.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: CD8-Positive T-Lymphocytes / Neoplasms Limits: Animals / Humans Language: En Journal: Cell Year: 2023 Document type: Article
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: CD8-Positive T-Lymphocytes / Neoplasms Limits: Animals / Humans Language: En Journal: Cell Year: 2023 Document type: Article