IL4 from T Follicular Helper Cells Downregulates Antitumor Immunity.
IL4 from T Follicular Helper Cells Downregulates Antitumor Immunity.
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DOI：
10.1158/2326-6066.cir-16-0113
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发表时间：
2017-01
影响因子：
10.1
通讯作者：
Ishioka C
中科院分区：
文献类型：
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作者：
Shirota H;Klinman DM;Ito SE;Ito H;Kubo M;Ishioka C
免疫细胞构成肿瘤微环境的大部分并调节肿瘤进展。临床数据表明，慢性炎症存在于肿瘤部位，特别是IL 4被上调。在这里，我们证明了T滤泡辅助（Tfh）细胞出现在肿瘤引流淋巴结，在那里他们产生了丰富的IL 4。表达IL4的Tfh细胞的缺失提高抗肿瘤免疫力，延迟肿瘤生长，并减少淋巴结中免疫抑制性骨髓细胞的产生。这些发现表明，来自Tfh细胞的IL 4影响抗肿瘤免疫，并构成一个有吸引力的治疗靶点，以减少肿瘤微环境中的免疫抑制，从而提高癌症免疫治疗的疗效。
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.