Mutant p53 gain of function mediates cancer immune escape that is counteracted by APR-246.

ABSTRACT:

Background

p53 mutants contribute to the chronic inflammatory tumour microenvironment (TME). In this study, we address the mechanism of how p53 mutants lead to chronic inflammation in tumours and how to transform it to restore cancer immune surveillance.

Methods

Our analysis of RNA-seq data from The Cancer Genome Atlas Breast Invasive Carcinoma (TCGA-BRCA) project revealed that mutant p53 (mtp53) cancers correlated with chronic inflammation. We used cell-based assays and a mouse model to discover a novel gain of function of mtp53 and the effect of the mtp53 reactivating compound APR-246 on the anti-tumour immune response.

Results

We found that tumour samples from patients with breast carcinoma carrying mtp53 showed elevated Interferon (IFN) signalling, Tumour Inflamma

SUBMITTER: Zhou X 

PROVIDER: S-EPMC9681866 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature