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Tumor-derived soluble CD155 inhibits DNAM-1–mediated antitumor activity of natural killer cells
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,...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Rockefeller University Press
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7144518/ https://www.ncbi.nlm.nih.gov/pubmed/32040157 http://dx.doi.org/10.1084/jem.20191290 |
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author | Okumura, Genki Iguchi-Manaka, Akiko Murata, Rikito Yamashita-Kanemaru, Yumi Shibuya, Akira Shibuya, Kazuko |
author_facet | Okumura, Genki Iguchi-Manaka, Akiko Murata, Rikito Yamashita-Kanemaru, Yumi Shibuya, Akira Shibuya, Kazuko |
author_sort | Okumura, Genki |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-7144518 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-71445182020-04-14 Tumor-derived soluble CD155 inhibits DNAM-1–mediated antitumor activity of natural killer cells Okumura, Genki Iguchi-Manaka, Akiko Murata, Rikito Yamashita-Kanemaru, Yumi Shibuya, Akira Shibuya, Kazuko J Exp Med Brief Definitive Report 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. Rockefeller University Press 2020-02-10 /pmc/articles/PMC7144518/ /pubmed/32040157 http://dx.doi.org/10.1084/jem.20191290 Text en © 2020 Okumura et al. https://creativecommons.org/licenses/by/4.0/This article is available under a Creative Commons License (Attribution 4.0 International, as described at https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Brief Definitive Report Okumura, Genki Iguchi-Manaka, Akiko Murata, Rikito Yamashita-Kanemaru, Yumi Shibuya, Akira Shibuya, Kazuko Tumor-derived soluble CD155 inhibits DNAM-1–mediated antitumor activity of natural killer cells |
title | Tumor-derived soluble CD155 inhibits DNAM-1–mediated antitumor activity of natural killer cells |
title_full | Tumor-derived soluble CD155 inhibits DNAM-1–mediated antitumor activity of natural killer cells |
title_fullStr | Tumor-derived soluble CD155 inhibits DNAM-1–mediated antitumor activity of natural killer cells |
title_full_unstemmed | Tumor-derived soluble CD155 inhibits DNAM-1–mediated antitumor activity of natural killer cells |
title_short | Tumor-derived soluble CD155 inhibits DNAM-1–mediated antitumor activity of natural killer cells |
title_sort | tumor-derived soluble cd155 inhibits dnam-1–mediated antitumor activity of natural killer cells |
topic | Brief Definitive Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7144518/ https://www.ncbi.nlm.nih.gov/pubmed/32040157 http://dx.doi.org/10.1084/jem.20191290 |
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