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SMARCD1 is a dual regulator of PD-L1 expression and cell proliferation facilitating tumor evasion

ABSTRACT: Cancer cells often evade immune responses by overexpressing immune checkpoint regulators, such as PD-L1. Here we identify a subunit of mating-type switching /sucrose fermentation (SWI/SNF) complex as a factor that favors tumor evasion by a dual mechanism involving both the induction of PD-L1-mediated immune checkpoint responses and the tumor cell proliferation. SMARCD1 deficient cancer cells exhibit not only reduced PD-L1 expression in vitro but also significantly suppressed tumor growth. Mechanistically, SMARCD1 maintains chromatin accessibility at PD-L1 transcriptional regulatory element thereby promoting PD-L1 expression in cancer cells. Besides, SMARCD1 might promote cancer cell proliferation by effecting several pathways such as AI3K-Akt signaling pathways. Collectively, these studies uncover SMARCD1 as a promising target for colorectal cancer (CRC) treatment.

ORGANISM(S): Mus musculus

PROVIDER: GSE275535 | GEO | 2025/04/22

REPOSITORIES: GEO

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