Hedgehog signaling induces PD-L1 expression and tumor cell proliferation in gastric cancer.

ABSTRACT: Tumor cells expressing programmed cell death ligand 1 (PD-L1) interact with PD-1 on CD8+ cytotoxic T lymphocytes (CTLs) to inhibit CTL effector function. In gastric cancer, the mechanism regulating PD-L1 is unclear. The Hedgehog (Hh) signaling pathway is reactivated in various cancers including gastric. Here we tested the hypothesis that Hh-induced PD-L1 inactivates effector T cell function and allows gastric cancer cell proliferation. Mouse organoids were generated from tumors of a triple-transgenic mouse model engineered to express an activated GLI2 allele, GLI2A, in Lgr5-expressing stem cells, (mTGOs) or normal mouse stomachs (mGOs). Bone marrow-derived dendritic cells (DCs) were pulsed with conditioned media collected from normal (mGO^CM) or cancer (mTGO^CM) organoi

SUBMITTER: Chakrabarti J 

PROVIDER: S-EPMC6324774 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature