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Cancer Immunol Res. 2017 Jan;5(1):61-71. doi: 10.1158/2326-6066.CIR-16-0113. Epub 2016 Dec 5.

IL4 from T Follicular Helper Cells Downregulates Antitumor Immunity.

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Department of Clinical Oncology, Tohoku University Hospital, Sendai, Japan.
Cancer and Inflammation Program, National Cancer Institute, Frederick, Maryland.
Department of Clinical Oncology, Tohoku University Hospital, Sendai, Japan.
Department of Informative Clinical Medicine, Gifu University Graduate School of Medicine, Gifu, Japan.
Division of Molecular Pathology, Research Institute for Biological Science, Tokyo University of Science, Chiba, Japan.


Immune cells constitute a large fraction of the tumor microenvironment and modulate tumor progression. Clinical data indicate that chronic inflammation is present at tumor sites and that IL4 in particular is upregulated. Here, we demonstrate that T follicular helper (Tfh) cells arise in tumor-draining lymph nodes where they produce an abundance of IL4. Deletion of IL4-expressing Tfh cells improves antitumor immunity, delays tumor growth, and reduces the generation of immunosuppressive myeloid cells in the lymph nodes. These findings suggest that IL4 from Tfh cells affects antitumor immunity and constitutes an attractive therapeutic target to reduce immunosuppression in the tumor microenvironment, and thus enhance the efficacy of cancer immunotherapy. Cancer Immunol Res; 5(1); 61-71.

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