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

• DOI: 10.1158/2326-6066.c.6550341.v1
• Publication Date: 2023-04-04T19:39:51Z
• Authors: Lichen Jing; Mariliis Ott; Candice D. Church; Rima M. Kulikauskas; Dafina Ibrani; Jayasri G. Iyer; Olga K. Afanasiev; Aric Colunga; Maclean M. Cook; Hong Xie; Alexander L. Gren...; Kelly G. Paulson; Aude G. Chapuis; Shailender Bhatia; Paul Nghiem; David M. Koelle
• Keywords: Merkel cell polyomavirus; Merkel cell; Tumor-infiltrating lymphocytes

<div>Abstract<p>Merkel cell carcinoma (MCC) is often caused by persistent expression of Merkel polyomavirus (MCPyV) T-antigen (T-Ag). These non-self proteins comprise about 400 amino acids (AA). Clinical responses to immune checkpoint inhibitors, seen in half patients, may relate T-Ag–specific T cells. Strategies increase CD8<sup>+</sup> T-cell number, breadth, or function could augment inhibition, but vaccines immunity must avoid delivery oncogenic domains. We probed MCC tumor-infiltrating lymphocytes (TIL) with an artificial antigen-presenting (aAPC) system and confirmed T-Ag recognition synthetic peptides, HLA-peptide tetramers, dendritic cells (DC). TILs from 9 12 (75%) subjects contained recognizing 1–8 MCPyV epitopes per person. Analysis 16 TIL prior data indicated that 97% patients MCPyV<sup>+</sup> had HLA alleles the genetic potential restrict T-Ag. The LT AA 70–110 region was epitope rich, whereas domains were not commonly recognized. Specific T-Ag–expressing DCs documented. Recovery oncoprotein–specific most tumors antigen indifference unlikely be a major cause inhibition failure. myriad restricted diverse indicates vaccination can rational component immunotherapy if tumor suppression overcome, regions modified without impacting immunogenicity.</p></div>