| First Author | Zhang Q | Year | 2015 |
| Journal | Cancer Res | Volume | 75 |
| Issue | 20 | Pages | 4312-21 |
| PubMed ID | 26249173 | Mgi Jnum | J:225872 |
| Mgi Id | MGI:5694859 | Doi | 10.1158/0008-5472.CAN-14-3590 |
| Citation | Zhang Q, et al. (2015) CCL5-Mediated Th2 Immune Polarization Promotes Metastasis in Luminal Breast Cancer. Cancer Res 75(20):4312-21 |
| abstractText | The tumor-promoting chemokine CCL5 has been implicated in malignant transformation of breast epithelial cells, with studies to date focusing mainly on basal-type breast cancers. In this study, we investigated the consequences of CCL5 deletion in the MMTV-PyMT transgenic mouse model of luminal breast cancer. In this model, primary tumor burden and pulmonary metastases were reduced significantly in CCL5-deficient subjects, an effect found to be associated with a deficit of Th2 (IL4(+)CD4(+) T) cells. Mechanistic investigations revealed that CCL5 activates CCR3, a highly expressed chemokine receptor on CD4(+) T cells, and also boosts Gfi1 expression to promote the differentiation of Th2 cells, which enhance the prometastatic activity of tumor-associated myeloid cells. Clinically, polarization toward this immunosuppressive Th2 phenotype was also evident in patients with advanced luminal breast cancer. Thus, our findings showed that CCL5/CCR3 signaling promotes metastasis by inducing Th2 polarization of CD4(+) T cells, with implications for prognosis and immunotherapy of luminal breast cancer. Cancer Res; 75(20); 4312-21. (c)2015 AACR. |
