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

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. To investigate the function of SMARCD1 in tumor cells, we established MC38 cell lines in which each target gene has been knocked out by sgRNA.