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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,...

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Autores principales: Okumura, Genki, Iguchi-Manaka, Akiko, Murata, Rikito, Yamashita-Kanemaru, Yumi, Shibuya, Akira, Shibuya, Kazuko
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Rockefeller University Press 2020
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.
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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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