Muscleblind-like proteins are novel modulators of the tumor-immune microenvironment

Exploiting the immune system to target and eradicate cancer cells is an area of intense clinical study. However, the underlying mechanisms that shape the tumor-immune microenvironment remain poorly understood. Here, we identify Muscleblind-like (MBNL) proteins as novel modulators of the tumor microenvironment across diverse cancer types. Initially, in a mouse melanoma model, we demonstrate that loss of MBNL expression drives reduced cytotoxic CD8+ T cell tumor infiltrate and increased tumor cell viability. This causes an attenuated response to inflammatory stimulation with interferon gamma and concomitantly reduced antigen presentation by MHC Class I. We then extended these studies to 29 human cancer types from extensive analysis of TCGA to find that high MBNL1 expression was consistently associated with augmented cytotoxic T cell tumor infiltration. These new insights position MBNL proteins as critical players shaping the immune landscape across diverse malignancies. RNA-Seq raw data from CRISPR edited C57BL/6 mouse cells with or without IFNg stimulation including the following genotypes: no-template control (NTC) or double knock out of MBNL1 and MBNL2 (DKO). N = 3 replicates for each condition.