Syndecan-1 inhibition promotes antitumor immune response and facilitates the efficacy of anti-PD1 checkpoint immunotherapy.

ABSTRACT: Tumor cell-originated events prevent efficient antitumor immune response and limit the application of anti-PD1 checkpoint immunotherapy. We show that syndecan-1 (SDC1) has a critical role in the regulation of T cell-mediated control of tumor growth. SDC1 inhibition increases the permeation of CD8⁺ T cells into tumors and triggers CD8⁺ T cell-mediated control of tumor growth, accompanied by increased proportions of progenitor-exhausted and effector-like CD8⁺ T cells. SDC1 deficiency alters multiple signaling events in tumor cells, including enhanced IFN-γ-STAT1 signaling, and augments antigen presentation and sensitivity to T cell-mediated cytotoxicity. Combinatory inhibition of SDC1 markedly potentiates the therapeutic effects of anti-PD1 in inhibiting tumo

SUBMITTER: Liu Y 

PROVIDER: S-EPMC11389782 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature