Increased T-cell Infiltration Elicited by Deletion in a -Deficient Mouse Model of Prostate Carcinogenesis.

Prostate cancer does not appear to respond to immune checkpoint therapies where T-cell infiltration may be a key limiting factor. Here, we report evidence that ablating the growth regulatory kinase can increase T-cell infiltration in an established -deficient mouse model of human prostate cancer. Mice that were doubly mutant in prostate tissue for and (prostate DKO) exhibited a markedly increased median survival with reduced tumor size and proliferation compared with control -mutant mice, the latter of which exhibited increased mRNA expression. A comparative transcriptomic analysis revealed upregulation in prostate DKO mice of the chemokines and , two potent chemoattractants for T lymphocytes. Consistent with this effect, we observed a relative increase in a predominantly CD4 T-cell infiltrate in the prostate epithelial and stroma of tumors from DKO mice. Collectively, our results offer a preclinical proof of concept for ERK5 as a target to enhance T-cell infiltrates in prostate cancer, with possible implications for leveraging immune therapy in this disease. .