Co-expression of CD39 and CD103 identifies tumor-reactive CD8 T cells in human solid tumors

• Published in: Nature communications Vol. 9; no. 1; pp. 2724 - 13
• Main Authors: Duhen, Thomas, Duhen, Rebekka, Montler, Ryan, Moses, Jake, Moudgil, Tarsem, de Miranda, Noel F., Goodall, Cheri P., Blair, Tiffany C., Fox, Bernard A., McDermott, Jason E., Chang, Shu-Ching, Grunkemeier, Gary, Leidner, Rom, Bell, Richard Bryan, Weinberg, Andrew D.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 13.07.2018; Nature Publishing Group; Nature Portfolio
• Subjects: 13/106; 13/31; 38/22; 38/61; 45/90; 631/250/1619/554/1834; 631/250/2152/1566/1571; 631/250/251; 631/67/580; 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; BASIC BIOLOGICAL SCIENCES; Cancer; Carcinoma, Squamous Cell - genetics; Carcinoma, Squamous Cell - immunology; Carcinoma, Squamous Cell - mortality; Carcinoma, Squamous Cell - pathology; CD103 antigen; CD8 antigen; CD8 Antigens - genetics; CD8 Antigens - immunology; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - pathology; Female; Head; Head & neck cancer; Humanities and Social Sciences; Humans; Immunophenotyping; Immunotherapy; Integrin alpha Chains - genetics; Integrin alpha Chains - immunology; Lymphocytes; Lymphocytes T; Lymphocytes, Tumor-Infiltrating - immunology; Lymphocytes, Tumor-Infiltrating - pathology; Major histocompatibility complex; Male; Melanoma - genetics; Melanoma - immunology; Melanoma - mortality; Melanoma - pathology; Metastases; multidisciplinary; Ovarian Neoplasms - genetics; Ovarian Neoplasms - immunology; Ovarian Neoplasms - mortality; Ovarian Neoplasms - pathology; Patients; Phenotypes; Receptors, Antigen, T-Cell, alpha-beta - genetics; Receptors, Antigen, T-Cell, alpha-beta - immunology; Science; Science (multidisciplinary); Solid tumors; 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; T cell receptors; Transcriptome; Tumor cells; Tumors
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-018-05072-0

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. Identifying and enumerating tumor-specific CD8 T cells are important for assessing cancer prognosis and therapy efficacy. Here the authors show that CD39 and CD103 mark a subset of tumor-infiltrating CD8 T cells that are tumor-reactive and exhibit characteristics of exhausted or tissue-resident memory T cells.