Tumor-derived soluble CD155 inhibits DNAM-1–mediated antitumor activity of natural killer cells

Journal: Journal of Experimental Medicine

Published: 2020-04-06

DOI: 10.1084/jem.20191290

Affiliations: 6

Authors: 6

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Research Highlight

Cancer-secreted protein shuts down anti-tumour immunity



Drugs that target the soluble form of a protein called CD155 could help enhance the anti-tumour activity of the immune system’s natural killer cells.

Researchers from the University of Tsukuba in Japan engineered mouse melanoma cells to produce soluble CD155, a protein expressed by many tumour types.

In its membrane-bound form, CD155 normally interacts with a receptor called DNAM-1 to enhance the anti-cancer activity of various immune cells, including natural killer cells. But in its soluble form, the team showed, CD155 interferes with the usual DNAM-1–mediated ability of natural killer cells to transfer cytotoxic materials into tumour cells.

As a result, the soluble CD155–producing melanoma cells grew more readily in the lungs of mice compared to cancer cells that could not make this protein.

“These are striking results that show how a single protein can drastically change the fate of a tumour,” said senior study author Kazuko Shibuya in a press release.

Supported content

  1. Journal of Experimental Medicine 217, e20191290 (2020). doi: 10.1084/jem.20191290
Institutions Share
Laboratory of Immunology, University of Tsukuba, Japan 0.47
Faculty of Medicine, University of Tsukuba, Japan 0.17
R&D Center for Innovative Drug Discovery, University of Tsukuba, Japan 0.14
Graduate School of Comprehensive Human Sciences, University of Tsukuba, Japan 0.08
School of Integrative and Global Majors (SIGMA), University of Tsukuba, Japan 0.08
Life Science Center for Survival Dynamics, Tsukuba Advanced Research Alliance (LS-TARA Center), University of Tsukuba, Japan 0.06