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

© JUAN GAERTNER/SCIENCE PHOTO LIBRARY/Getty

© JUAN GAERTNER/SCIENCE PHOTO LIBRARY/Getty

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.

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  1. Journal of Experimental Medicine 217, e20191290 (2020). doi: 10.1084/jem.20191290
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University of Tsukuba, Japan 1

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