DNAM-1 promotes inflammation-driven tumor development via enhancing IFN-γ production
DNAM-1 promotes inflammation-driven tumor development via enhancing IFN-γ production
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DNAM-1 通过增强 IFN-γ 的产生促进炎症驱动的肿瘤发展
DOI：
10.1093/intimm/dxab099
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发表时间：
2021
期刊：
影响因子：
4.4
通讯作者：
Shibuya K.
中科院分区：
文献类型：
--
作者：
Nakamura-Shinya Y;Iguchi-Manaka A;Murata R;Sato K;Van Vo A;Kanemaru K;Shibuya A;Shibuya K.
DNAM-1是T细胞和自然杀伤（NK）细胞上的活化免疫受体。其配体CD 155和CD 112的表达水平在肿瘤细胞上上调。CD 8 +T细胞和NK细胞上的DNAM-1与肿瘤细胞上的配体相互作用在肿瘤免疫中起重要作用。我们先前报道了DNAM-1缺陷的小鼠表现出由化学致癌物7，12-二甲基苯并[a]蒽（DMBA）诱导的肿瘤加速生长。与这些结果相反，我们在这里表明，由12-O-十四酰基佛波醇-13-乙酸酯（TPA）与DMBA一起诱导的肿瘤发展在DNAM-1缺陷小鼠中受到抑制。在该模型中，DNAM-1增强了常规CD 4 +T细胞的IFN-γ分泌，以促进炎症相关的肿瘤发展。这些发现表明，在炎症条件下，DNAM-1通过传统的CD 4 +T细胞促进肿瘤的发展。
DNAM-1 is an activating immunoreceptor on T cells and natural killer (NK) cells. Expression levels of its ligands, CD155 and CD112, are up-regulated on tumor cells. The interaction of DNAM-1 on CD8+T cells and NK cells with the ligands on tumor cells plays an important role in tumor immunity. We previously reported that mice deficient in DNAM-1 showed accelerated growth of tumors induced by the chemical carcinogen 7,12-dimethylbenz[a]anthracene (DMBA). Contrary to those results, we show here that tumor development induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) together with DMBA was suppressed in DNAM-1–deficient mice. In this model, DNAM-1 enhanced IFN-γ secretion from conventional CD4+T cells to promote inflammation-related tumor development. These findings suggest that, under inflammatory conditions, DNAM-1 contributes to tumor development via conventional CD4+T cells.