Epigenetic silencing by SETDB1 suppresses tumour intrinsic immunogenicity.

ABSTRACT: Epigenetic dysregulation is a defining feature of tumorigenesis that is implicated in immune escape^1,2. Here, to identify factors that modulate the immune sensitivity of cancer cells, we performed in vivo CRISPR-Cas9 screens targeting 936 chromatin regulators in mouse tumour models treated with immune checkpoint blockade. We identified the H3K9 methyltransferase SETDB1 and other members of the HUSH and KAP1 complexes as mediators of immune escape^3-5. We also found that amplification of SETDB1 (1q21.3) in human tumours is associated with immune exclusion and resistance to immune checkpoint blockade. SETDB1 represses broad domains, primarily within the open genome compartment. These domains are enriched for transposable elements (TEs) and immune clusters associated with

SUBMITTER: Griffin GK 

PROVIDER: S-EPMC9166167 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature