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.
This review aims to summarize the current knowledge of molecular pathways and their clinical relevance in melanoma.,Metastatic melanoma was a grim diagnosis, but in recent years tremendous advances have been made in treatments.,Chemotherapy provided little benefit in these patients, but development of targeted and new immune approaches made radical changes in prognosis.,This would not have happened without remarkable advances in understanding the biology of disease and tremendous progress in the genomic (and other “omics”) scale analyses of tumors.,The big problems facing the field are no longer focused exclusively on the development of new treatment modalities, though this is a very busy area of clinical research.,The focus shifted now to understanding and overcoming resistance to targeted therapies, and understanding the underlying causes of the heterogeneous responses to immune therapy.