HNRNPC suppresses tumor immune microenvironment by activating Treg cells promoting the progression of prostate cancer

Immune microenvironment could affect the biological progress in prostate cancer (PCa) through N6 methyl adenosine (m6A) methylation. The purpose of this study was to investigate the crosstalk between m6A methylation and immune microenvironment and explore potential biomarkers to improve the immunotherapeutic response. Firstly, according to 11 differentially expressed m6A genes between normal and tumor samples, PCa patients were divided into immune microenvironment subtype 1 (IMS1) and IMS2 based on m6A gene profiles extracted from The Cancer Genome Atlas (TCGA) database. IMS2 showed an immune cold phenotype with worse prognoses, and HNRNPC was identified as the biomarker of IMS2 by the protein-protein interaction network. Furthermore, through bioinformatics analyses and in vitro experiments, we found that HNRNPC-high patients showed a suppressive immune-infiltrating tumor microenvironment with a higher infiltration of regulatory T (Treg) cells. Finally, we cocultured transfected PCa cells with peripheral blood mononuclear cells (PBMC) and verified that HNRNPC inhibits tumor immunity by elevating the activation of Treg cells and suppression of effector CD8 T cell. In conclusion, we identified a cold immune phenotype in PCa, and HNRNPC regulating the activation of Treg cells. Activation of the immune microenvironment through targeting HNRNPC may be a potential therapeutic option for advanced PCa.

Automated summary

The study investigates the relationship between N6 methyl adenosine (m6A) methylation and immune microenvironment in prostate cancer (PCa), aiming to identify potential biomarkers for improving immunotherapeutic response. Based on the m6A gene profiles extracted from The Cancer Genome Atlas (TCGA) database, PCa patients were divided into two immune microenvironment subtypes, with IMS2 showing a worse prognosis. HNRNPC was identified as the biomarker for IMS2 and found to inhibit tumor immunity by elevating the activation of regulatory T cells and suppressing effector CD8 T cell. Targeting HNRNPC to activate the immune microenvironment could be a potential therapeutic option for advanced PCa.