Prevalent and Diverse Intratumoral Oncoprotein-Specific CD8⁺ T Cells within Polyomavirus-Driven Merkel Cell Carcinomas.

ABSTRACT: Merkel cell carcinoma (MCC) is often caused by persistent expression of Merkel cell polyomavirus (MCPyV) T-antigen (T-Ag). These non-self proteins comprise about 400 amino acids (AA). Clinical responses to immune checkpoint inhibitors, seen in about half of patients, may relate to T-Ag-specific T cells. Strategies to increase CD8⁺ T-cell number, breadth, or function could augment checkpoint inhibition, but vaccines to augment immunity must avoid delivery of oncogenic T-antigen domains. We probed MCC tumor-infiltrating lymphocytes (TIL) with an artificial antigen-presenting cell (aAPC) system and confirmed T-Ag recognition with synthetic peptides, HLA-peptide tetramers, and dendritic cells (DC). TILs from 9 of 12 (75%) subjects contained CD8⁺ T cells recognizing 1-8 MC

SUBMITTER: Jing L 

PROVIDER: S-EPMC7196523 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature