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Updated: Mar 2, 2026
An Orthotopic Murine Model of Human Prostate Cancer Metastasis
Published on: September 18, 2013
Increased T-cell Infiltration Elicited by Erk5 Deletion in a Pten-Deficient Mouse Model of Prostate Carcinogenesis
Carolyn J Loveridge1,2, Ernest J Mui2, Rachana Patel2
1Institute of Cancer Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Bearsden, Glasgow, United Kingdom.
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.
Insights
Targeting Erk5 in prostate cancer may enhance T-cell infiltration, a crucial factor for immune checkpoint therapies. Ablating Erk5 in a mouse model improved survival and increased T-cell presence in tumors.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- Prostate cancer often shows poor response to immune checkpoint therapies.
- Limited T-cell infiltration is a key factor hindering treatment efficacy.
- Erk5 (Extracellular signal-regulated kinase 5) is a growth regulatory kinase.
Purpose of the Study:
- To investigate the role of Erk5 in modulating T-cell infiltration in prostate cancer.
- To evaluate the therapeutic potential of targeting Erk5 in a preclinical mouse model.
Main Methods:
- Utilized a Pten-deficient mouse model of prostate cancer.
- Generated double mutant mice lacking Erk5 in prostate tissue (prostate DKO).
- Performed comparative transcriptomic analysis and assessed T-cell infiltration.
Main Results:
- Prostate DKO mice showed significantly increased median survival, reduced tumor size, and lower proliferation.
- Upregulation of chemokines Ccl5 and Cxcl10 was observed in DKO mice.
- A notable increase in CD4+ T-cell infiltration was found in tumors of DKO mice.
Conclusions:
- Erk5 ablation enhances T-cell infiltration in a prostate cancer mouse model.
- This suggests Erk5 is a potential therapeutic target to improve immune therapy response in prostate cancer.
- Results provide a preclinical proof of concept for targeting ERK5 to boost anti-tumor immunity.
