Combination of chemotherapy and PD-1 blockade induces T cell responses to tumor non-mutated neoantigens.

ABSTRACT: Here, we developed an unbiased, functional target-discovery platform to identify immunogenic proteins from primary non-small cell lung cancer (NSCLC) cells that had been induced to apoptosis by cisplatin (CDDP) treatment in vitro, as compared with their live counterparts. Among the multitude of proteins identified, some of them were represented as fragmented proteins in apoptotic tumor cells, and acted as non-mutated neoantigens (NM-neoAgs). Indeed, only the fragmented proteins elicited effective multi-specific CD4⁺ and CD8⁺ T cell responses, upon a chemotherapy protocol including CDDP. Importantly, these responses further increased upon anti-PD-1 therapy, and correlated with patients' survival and decreased PD-1 expression. Cross-presentation assays showed that NM-ne

SUBMITTER: Grimaldi A 

PROVIDER: S-EPMC7042341 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature