Department of Immunology, University of Tsukuba, Tsukuba, Ibaraki, Japan.
Doctoral Program of Biomedical Sciences, Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan.
J Exp Med. 2020 Mar 2;217(4):1. doi: 10.1084/jem.20191290.
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.
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，人细胞表达膜结合型 CD155 和由 CD155 剪接异构体编码的可溶性 CD155（sCD155）。然而，sCD155 在肿瘤免疫中的作用尚不清楚。在这里，我们发现，在静脉注射产生 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多于注射亲本 B16/BL6 黑色素瘤后。NK 细胞耗竭消除了 WT 小鼠中肿瘤集落数量的差异。体外实验表明，sCD155 干扰了 DNAM-1 介导的 NK 细胞脱颗粒。此外，DNAM-1 对 sCD155 的亲和力大于 TIGIT 和 CD96，表明 sCD155 优先与 DNAM-1 结合。综上所述，这些结果表明 sCD155 抑制了 NK 细胞的 DNAM-1 介导的细胞毒性活性，从而促进了 B16/BL6 黑色素瘤在肺部的定植。
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