PD-1 combination therapy with IL-2 modifies CD8⁺ T cell exhaustion program.

ABSTRACT: Combination therapy with PD-1 blockade and IL-2 is highly effective during chronic lymphocytic choriomeningitis virus infection¹. Here we examine the underlying basis for this synergy. We show that PD-1 + IL-2 combination therapy, in contrast to PD-1 monotherapy, substantially changes the differentiation program of the PD-1⁺TCF1⁺ stem-like CD8⁺ T cells and results in the generation of transcriptionally and epigenetically distinct effector CD8⁺ T cells that resemble highly functional effector CD8⁺ T cells seen after an acute viral infection. The generation of these qualitatively superior CD8⁺ T cells that mediate viral control underlies the synergy between PD-1 and IL-2. Our results show that the PD-1⁺TC

SUBMITTER: Hashimoto M 

PROVIDER: S-EPMC9793890 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature