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@ARTICLE{Sektioglu:119361,
author = {I. M. Sektioglu$^*$ and R. Carretero$^*$ and N. Bulbuc$^*$
and T. Bald and T. Tüting and A. Y. Rudensky and G.
Hämmerling$^*$},
title = {{B}asophils {P}romote {T}umor {R}ejection via {C}hemotaxis
and {I}nfiltration of {CD}8+ {T} {C}ells.},
journal = {Cancer research},
volume = {77},
number = {2},
issn = {1538-7445},
address = {Philadelphia, Pa.},
publisher = {AACR},
reportid = {DKFZ-2017-00116},
pages = {291 - 302},
year = {2017},
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.},
cin = {G181 / D121 / D030},
ddc = {610},
cid = {I:(DE-He78)G181-20160331 / I:(DE-He78)D121-20160331 /
I:(DE-He78)D030-20160331},
pnm = {314 - Tumor immunology (POF3-314)},
pid = {G:(DE-HGF)POF3-314},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:27879269},
doi = {10.1158/0008-5472.CAN-16-0993},
url = {https://inrepo02.dkfz.de/record/119361},
}