Emergence Of High-Avidity Melan-A-Specific Clonotypes As A Reflection Of Anti-Pd-1 Clinical Efficacy

Therapeutic strategies using anti-PD-1-blocking antibodies reported unparalleled effectiveness for melanoma immunotherapy, but deciphering immune responses modulated by anti-PD-1 treatment remains a crucial issue. Here, we analyzed the composition and functions of the large Melan-A-specific T-cell repertoire in the peripheral blood of 9 melanoma patients before and after 2 months of treatment with anti-PD-1. We observed amplification of Melan-A-specific V beta subfamilies undetectable before therapy (thereafter called emerging V beta subfamilies) in responding patients, with a predominant expansion in patients with a complete response. These emerging V beta subfamilies displayed a higher functional avidity for their cognate antigen than V beta subfamilies not amplified upon anti-PD-1 therapy and could be identified by a sustained coexpression of PD-1 and TIGIT receptors. Thus, in addition to the emergence of neoantigen-specific T cells previously documented upon anti-PD-1 therapy, our work describes the emergence of high-avidity Melan-A-specific clonotypes as a surrogate marker of treatment efficacy. (C) 2017 AACR.