Journal Article

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

Duhen, Rebekka, Weinberg, Andrew D., Bell, Richard Bryan, McDermott, Jason E., Fox, Bernard A., Chang, Shu-Ching, Montler, Ryan, Duhen, Thomas, Moudgil, Tarsem, Grunkemeier, Gary, Goodall, Cheri P., Leidner, Rom, Blair, Tiffany C., Moses, Jake, de Miranda, Noel F.

2018

Overview

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.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 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