| First Author | Deng S | Year | 2019 |
| Journal | Cancer Lett | Volume | 443 |
| Pages | 1-12 | PubMed ID | 30481563 |
| Mgi Jnum | J:268372 | Mgi Id | MGI:6271148 |
| Doi | 10.1016/j.canlet.2018.11.017 | Citation | Deng S, et al. (2019) Non-platelet-derived CXCL4 differentially regulates cytotoxic and regulatory T cells through CXCR3 to suppress the immune response to colon cancer. Cancer Lett 443:1-12 |
| abstractText | CXCL4 is mainly produced by activated platelets, and certain somatic cells and cancer cells also express CXCL4. However, the physiological function of non-platelet-derived CXCL4 is unclear. Previously, we reported that CXCL4 produced by cancer cells accelerated tumor growth by suppressing the antitumor activities of cytotoxic T lymphocytes (CTLs). To elucidate the mechanism of CXCL4 in tumor immunity, we compared the CTLs and regulatory T cells (Tregs) from CXCL4(-/-), CXCR3(-/-) and C57BL/6 mice overexpressing CXCL4 via intramuscular electroporation. CXCL4 accelerated tumor growth in CXCL4(-/-) and C57BL/6 mice but not in CXCR3(-/-) mice. Furthermore, CXCL4 decreased CTLs proliferation and IFN-gamma production and enhanced CTLs apoptosis and programmed death 1 (PD-1) expression. Conversely, CXCL4 promoted Tregs proliferation and TGF-beta production and downregulated PD-1 expression in Tregs. Notably, these effects of CXCL4 were both observed in the splenic and tumor-infiltrating CTLs and Tregs from wild-type but not CXCR3(-/-) mice. Thus, we revealed a negative immune regulatory function for non-platelet-derived CXCL4 through CXCR3 that cancer cells could hijack to evade the host immune system, suggesting that the CXCL4/CXCR3 axis may serve as a novel target for colorectal cancer immunotherapy. |
