T cell priming by high avidity neoantigens in lymph nodes augments adoptive immunotherapy.

ABSTRACT: Adoptive transfer of T lymphocytes specific for tumor-associated neoantigens can elicit immunity against solid tumors in patients. However, how these antigens impact T cell function, effector differentiation, and persistence remains unclear. We examined how an identical CD8+ T cell product was shaped by melanoma expressing either a low-avidity tumor-associated antigen or high-avidity neoantigen, and kinetically profiled T cell differentiation in these two contexts across host tissues. High-avidity neoantigen expression was sufficient to activate naïve CD8+ T cells - leading to robust tumor regression and long-term protective immunity upon tumor rechallenge. Mechanistically, transferred naïve CD8+ T cells reacting to high-avidity neoantigen exhibited enhanced cytokine production, heightened

SUBMITTER: Wittling MC 

PROVIDER: S-EPMC12802582 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature