ATR Mutations Promote the Growth of Melenama Tumor by Modulating the Immune Microenvironment [tumor]. Mus musculus

Melanomas accumulate a high burden of mutations that could potentially generate neoantigens, yet these tumors are still able to suppress the immune response in order to facilitate their continued growth. In this study, we identify subsets of human melanoma tumors that have partial loss of function mutations in ATR, a kinase that recognizes and repairs UV-induced DNA damage and is required for cellular proliferation. ATR mutant tumors exhibit both the accumulation of multiple mutations and the altered expression of inflammatory genes, resulting in decreased T-cell recruitment and increased recruitment of macrophages known to spur tumor invasion. Taken together, these studies identify a novel mechanism by which melanoma cells modulate the immune microenvironment to allow continued tumor growth. Overall design: RNA-sequencing analysis was performed on ATR wild type and ATR mutant mouse nevi. 3 control (ATR wild type) and 3 experimental (ATR mutant mouse nevi) samples were compared.