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Cancer Res. 2017 Jan 15;77(2):291-302. doi: 10.1158/0008-5472.CAN-16-0993. Epub 2016 Nov 22.

Basophils Promote Tumor Rejection via Chemotaxis and Infiltration of CD8+ T Cells.

Author information

1
Division of Molecular Immunology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
2
Department of Dermatology, University Hospital Magdeburg, Magdeburg, Germany.
3
Immunology Program, Howard Hughes Medical Institute and Memorial Sloan Kettering Cancer Center, New York, New York.
4
Division of Immunogenetics, German Cancer Research Center (DKFZ), Heidelberg, Germany. hammerling@dkfz.de.

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.

PMID:
27879269
DOI:
10.1158/0008-5472.CAN-16-0993
[Indexed for MEDLINE]
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