@misc{10481/107655,
year = {2017},
month = {1},
url = {https://hdl.handle.net/10481/107655},
abstract = {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.},
organization = {Wilhelm Sander Stiftung 2009.022.2},
organization = {German Cancer Research Center (DKFZ), Germany},
organization = {University Hospital Magdeburg, Germany},
organization = {Howard Hughes Medical Institute and Memorial Sloan Kettering Cancer Center, New York},
publisher = {American Association for Cancer Research},
keywords = {Cancer},
keywords = {Immunology},
keywords = {Basophil},
title = {Basophils Promote Tumor Rejection via Chemotaxis and Infiltration of CD8+ T Cells},
doi = {10.1158/0008-5472.CAN-16-0993},
author = {Sektioglu, Ibrahim M. and Carretero Coca, Rafael and Bulbuc, Nadja and Bald, Tobias and Tüting, Thomas and Rudensky, Alexander Y. and Hämmerling, Günter J.},
}