Send to

Choose Destination
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

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


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.

[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center