Publication Title
Nat Commun
Document Type
Article
Publication Date
7-13-2018
Keywords
Adenocarcinoma of Lung/genetics; Adenocarcinoma of Lung/immunology; Adenocarcinoma of Lung/mortality; Adenocarcinoma of Lung/pathology; Antigens, CD/genetics; Antigens, CD/immunology; Apyrase/genetics; Apyrase/immunology; CD8 Antigens/genetics; CD8 Antigens/immunology; CD8-Positive T-Lymphocytes/immunology; CD8-Positive T-Lymphocytes/pathology; Carcinoma, Squamous Cell/genetics; Carcinoma, Squamous Cell/immunology; Carcinoma, Squamous Cell/mortality; Carcinoma, Squamous Cell/pathology; Female; Humans; Immunophenotyping; Integrin alpha Chains/genetics; Integrin alpha Chains/immunology; Lymphocytes, Tumor-Infiltrating/immunology; Lymphocytes, Tumor-Infiltrating/pathology; Male; Melanoma/genetics; Melanoma/immunology; Melanoma/mortality; Melanoma/pathology; Ovarian Neoplasms/genetics; Ovarian Neoplasms/immunology; Ovarian Neoplasms/mortality; Ovarian Neoplasms/pathology; Receptors, Antigen, T-Cell, alpha-beta/genetics; Receptors, Antigen, T-Cell, alpha-beta/immunology; Squamous Cell Carcinoma of Head and Neck/genetics; Squamous Cell Carcinoma of Head and Neck/immunology; Squamous Cell Carcinoma of Head and Neck/mortality; Squamous Cell Carcinoma of Head and Neck/pathology; Survival Analysis; Transcriptome
Abstract
Identifying tumor antigen-specific T cells from cancer patients has important implications for immunotherapy diagnostics and therapeutics. Here, we show that CD103+CD39+ tumor-infiltrating CD8 T cells (CD8 TIL) are enriched for tumor-reactive cells both in primary and metastatic tumors. This CD8 TIL subset is found across six different malignancies and displays an exhausted tissue-resident memory phenotype. CD103+CD39+ CD8 TILs have a distinct T-cell receptor (TCR) repertoire, with T-cell clones expanded in the tumor but present at low frequencies in the periphery. CD103+CD39+ CD8 TILs also efficiently kill autologous tumor cells in a MHC-class I-dependent manner. Finally, higher frequencies of CD103+CD39+ CD8 TILs in patients with head and neck cancer are associated with better overall survival. Our data thus describe an approach for detecting tumor-reactive CD8 TILs that will help define mechanisms of existing immunotherapy treatments, and may lead to future adoptive T-cell cancer therapies.
Clinical Institute
Cancer
Specialty/Research Institute
Oncology
Specialty/Research Institute
Earle A. Chiles Research Institute
