P04.02 Diversity of CD4+ blood T-cell clonality predicts longer survival with CTLA4 or PD-1 checkpoint inhibition in advanced melanoma

Background T cells play a central role in tumor immunity. In principle, cell requires antigen recognition by T-cell receptor (TCR) to gain effector function. Antigen-driven activation leads clonal expansion with generation of progeny that all express the same chronotypic TCR. This makes TCR analysis useful tool comprehensively and individually understand antigen-specific responses. Indeed, we previously showed repertoires CD8 + but not CD4 are restricted many clones blood psoriasis patients. Together strong genetic association HLA-C*06:02 causing an autoimmune response against melanocytes psoriasis, our results from analyses clearly indicate pathogenesis psoriasis. Patients Methods Here, utilize expertise how anti-tumor responses affect clinical immune-related adverse events (irAEs) therapeutic checkpoint inhibitions. We analyzed melanoma patients upon blockade cytotoxic T-lymphocyte-associated protein 4 (CTLA4) or programmed death 1 (PD-1) using Vβ-gene spectratyping. Results Surprisingly, observed variable levels restriction extensive restrictions compared healthy controls. indicates presence substantial numbers prior initiation immunotherapy. The detected were enriched tumor-infiltrating lymphocytes (TILs). suggests melanoma-reactive circulate more frequently patients, although it is generally assumed tumor-specific only detectable TILs. Greater diversification particularly before immunotherapy correlated long-term survival after CTLA4 PD-1 inhibition. who developed severe during blockade, newly expanded clones, suggesting emerged contributed these irAEs. Conclusions Our data demonstrate diversity circulation may reflect anti-melanoma study provides rationale for predicting inhibitors patient’s blood, also emphasizes importance cell-mediated immunity melanoma. Disclosure Information A. Arakawa: None. S. Vollmer: J. Tietze: B. Research Grant (principal investigator, collaborator consultant pending grants as well already received); Significant; BMS. D. Speakers Bureau/Honoraria (speakers bureau, symposia, expert witness); Modest; BMS, MSD, Novartis, Roche, Almiral. Galinski: M.V. Heppt: C. Berking: Amgen, AstraZeneca, Incyte, Merck, Pierre Fabre, Regeneron, Sanofi/Aventis. J.C. Prinz: