Mitigating non-genetic resistance to checkpoint inhibition based on multiple states of immune exhaustion.

ABSTRACT: Despite the revolutionary impact of immune checkpoint inhibition on cancer therapy, the lack of response in a subset of patients, as well as the emergence of resistance, remain significant challenges. Here we explore the theoretical consequences of the existence of multiple states of immune cell exhaustion on response to checkpoint inhibition therapy. In particular, we consider the emerging understanding that T cells can exist in various states: fully functioning cytotoxic cells, reversibly exhausted cells with minimal cytotoxicity, and terminally exhausted cells. We hypothesize that inflammation augmented by drug activity triggers transitions between these phenotypes, which can lead to non-genetic resistance to checkpoint inhibitors. We introduce a conceptual mathematical model, coupled w

SUBMITTER: Kareva I 

PROVIDER: S-EPMC10858190 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature