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01-10-2017 | Original Article

Blockade of CD112R and TIGIT signaling sensitizes human natural killer cell functions

Authors: Feng Xu, Alexander Sunderland, Yue Zhou, Richard D. Schulick, Barish H. Edil, Yuwen Zhu

Published in: Cancer Immunology, Immunotherapy | Issue 10/2017

Abstract

Trastuzumab is the first-line drug to treat breast cancer with high Her2 expression. However, many cancers failed to respond, largely due to their resistance to NK cell-triggered antibody-dependent cellular cytotoxicity (ADCC). Poliovirus receptor (PVR)-like molecules are known to be important for lymphocyte functions. We found that all PVR-like receptors are expressed on human NK cells, and only TIGIT is preferentially expressed on the CD16+ NK cell subset. Disrupting the interactions of PVR-like receptors with their ligands on cancer cells regulates NK cell activity. More importantly, TIGIT is upregulated upon NK cell activation via ADCC. Blockade of TIGIT or CD112R, separately or together, enhances trastuzumab-triggered antitumor response by human NK cells. Thus, our findings suggest that PVR-like receptors regulate NK cell functions and can be targeted for improving trastuzumab therapy for breast cancer.

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Title: Blockade of CD112R and TIGIT signaling sensitizes human natural killer cell functions
Authors: Feng Xu
Alexander Sunderland
Yue Zhou
Richard D. Schulick
Barish H. Edil
Yuwen Zhu
Publication date: 01-10-2017
Publisher: Springer Berlin Heidelberg
Published in: Cancer Immunology, Immunotherapy / Issue 10/2017
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-017-2031-x

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