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Tumor-derived soluble CD155 inhibits DNAM-1–mediated antitumor activity of natural killer cells
Journal of Experimental Medicine ( IF 12.6 ) Pub Date : 2020-02-10 , DOI: 10.1084/jem.20191290
Genki Okumura 1, 2 , Akiko Iguchi-Manaka 3 , Rikito Murata 1, 4 , Yumi Yamashita-Kanemaru 1 , Akira Shibuya 1, 5, 6 , Kazuko Shibuya 1, 6
Affiliation  

CD155 is a ligand for DNAM-1, TIGIT, and CD96 and is involved in tumor immune responses. Unlike mouse cells, human cells express both membranous CD155 and soluble CD155 (sCD155) encoded by splicing isoforms of CD155. However, the role of sCD155 in tumor immunity remains unclear. Here, we show that, after intravenous injection with sCD155-producing B16/BL6 melanoma, the numbers of tumor colonies in wild-type (WT), TIGIT knock-out (KO), or CD96 KO mice, but not DNAM-1 KO mice, were greater than after injection with parental B16/BL6 melanoma. NK cell depletion canceled the difference in the numbers of tumor colonies in WT mice. In vitro assays showed that sCD155 interfered with DNAM-1–mediated NK cell degranulation. In addition, DNAM-1 had greater affinity than TIGIT and CD96 for sCD155, suggesting that sCD155 bound preferentially to DNAM-1. Together, these results demonstrate that sCD155 inhibits DNAM-1–mediated cytotoxic activity of NK cells, thus promoting the lung colonization of B16/BL6 melanoma.

中文翻译:

肿瘤来源的可溶性 CD155 抑制 DNAM-1 介导的自然杀伤细胞的抗肿瘤活性

CD155 是 DNAM-1、TIGIT 和 CD96 的配体,参与肿瘤免疫反应。与小鼠细胞不同,人类细胞表达膜 CD155 和由 CD155 剪接亚型编码的可溶性 CD155 (sCD155)。然而,sCD155在肿瘤免疫中的作用仍不清楚。在这里,我们显示,静脉注射产生 sCD155 的 B16/BL6 黑色素瘤后,野生型 (WT)、TIGIT 敲除 (KO) 或 CD96 KO 小鼠中的肿瘤集落数量增加,但 DNAM-1 KO 小鼠中的肿瘤集落数量没有增加小鼠,比注射亲本 B16/BL6 黑色素瘤后更大。NK 细胞耗竭消除了 WT 小鼠肿瘤集落数量的差异。体外测定表明 sCD155 干扰 DNAM-1 介导的 NK 细胞脱颗粒。此外,DNAM-1对sCD155的亲和力比TIGIT和CD96更大,表明sCD155优先与DNAM-1结合。总之,这些结果表明 sCD155 抑制 DNAM-1 介导的 NK 细胞的细胞毒活性,从而促进 B16/BL6 黑色素瘤的肺部定植。
更新日期:2020-02-10
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