title: IL4 from T Follicular Helper Cells Downregulates Antitumor Immunity.
abstract: 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. ©2016 AACR.
authors.affiliation: Department of Clinical Oncology, Tohoku University Hospital, Sendai, Japan. hidekazu.shirota.e1@tohoku.ac.jp.
authors.forename: Hidekazu
authors.initials: H
authors.lastname: Shirota
authors.affiliation: Cancer and Inflammation Program, National Cancer Institute, Frederick, Maryland.
authors.forename: Dennis M
authors.initials: DM
authors.lastname: Klinman
authors.affiliation: Department of Clinical Oncology, Tohoku University Hospital, Sendai, Japan.
authors.forename: Shuku-Ei
authors.initials: SE
authors.lastname: Ito
authors.affiliation: Department of Informative Clinical Medicine, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Ito
authors.affiliation: Division of Molecular Pathology, Research Institute for Biological Science, Tokyo University of Science, Chiba, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Kubo
authors.affiliation: Department of Clinical Oncology, Tohoku University Hospital, Sendai, Japan.
authors.forename: Chikashi
authors.initials: C
authors.lastname: Ishioka
mesh_terms: D000818:Animals; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D015870:Gene Expression; D018858:Germinal Center / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D007109:Immunity; D015847:Interleukin-4 / Q000235:genetics / Q000378:metabolism*; D008198:Lymph Nodes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D009369:Neoplasms / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000378:metabolism*; D059016:Tumor Microenvironment / Q000235:genetics / Q000276:immunology
chemical_list: D016207:Cytokines; D015847:Interleukin-4