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

Overview

Journal Cancer Res

Specialty Oncology

Date 2017 May 19

PMID 28515147

Citations 15

Authors

Carolyn J Loveridge

Ernest J Mui

Rachana Patel

Ee Hong Tan

Imran Ahmad

Michelle Welsh

Julie Galbraith

Ann Hedley

Colin Nixon

Karen Blyth

Owen Sansom

Hing Y Leung

Affiliations

Soon will be listed here.

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 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. .

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