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| Home > Publications database > Basophils Promote Tumor Rejection via Chemotaxis and Infiltration of CD8+ T Cells. |
| Home > Publications database > Basophils Promote Tumor Rejection via Chemotaxis and Infiltration of CD8+ T Cells. |
| Journal Article | DKFZ-2017-00116 |
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2017
AACR
Philadelphia, Pa.
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Please use a persistent id in citations: doi:10.1158/0008-5472.CAN-16-0993
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. Cancer Res; 77(2); 291-302. ©2016 AACR.
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