| First Author | Sektioglu IM | Year | 2017 |
| Journal | Cancer Res | Volume | 77 |
| Issue | 2 | Pages | 291-302 |
| PubMed ID | 27879269 | Mgi Jnum | J:238426 |
| Mgi Id | MGI:5819315 | Doi | 10.1158/0008-5472.CAN-16-0993 |
| Citation | Sektioglu IM, et al. (2017) Basophils Promote Tumor Rejection via Chemotaxis and Infiltration of CD8+ T Cells. Cancer Res 77(2):291-302 |
| abstractText | Elevated numbers of regulatory T cells (Treg) in patient tumors are known to inhibit efficient antitumor T-cell responses. To study the mechanisms controlling tumor rejection, we assessed different mouse models for Treg depletion. In Foxp3DTR knock-in mice, about 99% Treg depletion was achieved, resulting in complete rejection of transplanted HCmel12 melanomas in a CD8+ T-cell-dependent way. In contrast, about 90% Treg depletion obtained in BAC transgenic Foxp3.LuciDTR4 mice failed to induce complete rejection of HCmel12 melanomas, demonstrating that residual Tregs were able to control CD8+ T-cell responses against the tumor. Ninety-nine percent of Treg depletion provoked drastic changes in the tumor microenvironment, such as strong infiltration of CD8+ T cells and basophils. Intratumoral basophils enhanced CD8+ T-cell infiltration via production of chemokines CCL3 and CCL4; antibody-based blocking of these chemokines inhibited CD8+ T-cell infiltration. Therapeutic induction of basophilia by IL3/anti-IL3 antibody complexes, combined with transfer of CD8+ T cells, resulted in enhanced T-cell infiltration and tumor rejection. Our study identifies a critical role basophils play in tumor rejection and that this role can be exploited for therapeutic intervention. Cancer Res; 77(2); 291-302. (c)2016 AACR. |
