Open AccessTumor-derived soluble CD155 inhibits DNAM-1–mediated antitumor activity of natural killer cells
Author(s) -
Genki Okumura,
Akiko Iguchi-Manaka,
Rikito Murata,
Yumi Yamashita-Kanemaru,
Akira Shibuya,
Kazuko Shibuya
Publication year - 2020
Publication title -
the journal of experimental medicine/the journal of experimental medicine
Language(s) - Uncategorized
Resource type - Journals
SCImago Journal Rank - 8.483
H-Index - 448
eISSN - 1540-9538
pISSN - 0022-1007
DOI - 10.1084/jem.20191290
Subject(s) - tigit , dnam , biology , degranulation , cytotoxic t cell , immune system , cancer research , immunology , natural killer cell , microbiology and biotechnology , in vitro , receptor , cd8 , biochemistry , gene expression , dna methylation , gene
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.