| First Author | Loveridge CJ | Year | 2017 |
| Journal | Cancer Res | Volume | 77 |
| Issue | 12 | Pages | 3158-3168 |
| PubMed ID | 28515147 | Mgi Jnum | J:242569 |
| Mgi Id | MGI:5905679 | Doi | 10.1158/0008-5472.CAN-16-2565 |
| Citation | Loveridge CJ, et al. (2017) Increased T-cell Infiltration Elicited by Erk5 Deletion in a Pten-Deficient Mouse Model of Prostate Carcinogenesis. Cancer Res 77(12):3158-3168 |
| abstractText | 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. (c)2017 AACR. |
