Increased T-cell Infiltration Elicited by Erk5 Deletion in a Pten -Deficient Mouse Model of Prostate Carcinogenesis

Cancer Research
Carolyn J LoveridgeHing Y Leung

Abstract

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 Erk5 can increase T-cell infiltration in an established Pten-deficient mouse model of human prostate cancer. Mice that were doubly mutant in prostate tissue for Pten and Erk5 (prostate DKO) exhibited a markedly increased median survival with reduced tumor size and proliferation compared with control Pten-mutant mice, the latter of which exhibited increased Erk5 mRNA expression. A comparative transcriptomic analysis revealed upregulation in prostate DKO mice of the chemokines Ccl5 and Cxcl10, 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. Cancer Res; 77(12); 3158-68. ©2017 AACR.

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Citations

Feb 28, 2018·Oncogene·Ignazia TusaElisabetta Rovida
Nov 20, 2019·Oncogene·Carolyn J LoveridgeHing Y Leung
Apr 25, 2020·British Journal of Cancer·Thiago VidottoJeremy A Squire
Apr 11, 2019·Nature Reviews. Drug Discovery·Willem J M MulderMihai G Netea
Mar 25, 2019·International Journal of Molecular Sciences·Barbara Stecca, Elisabetta Rovida
Jun 5, 2021·Journal of Cell Communication and Signaling·Arun J Singh, Joe W Gray

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