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01-03-2016 | Original Article

Immunoreceptor TIGIT inhibits the cytotoxicity of human cytokine-induced killer cells by interacting with CD155

Published in: Cancer Immunology, Immunotherapy | Issue 3/2016

Abstract

T cell Ig and ITIM domain (TIGIT) is a newly identified inhibitory receptor expressed on T and natural killer (NK) cells. Cytokine-induced killer (CIK) cells express CD3 and CD56 molecules, and share functional properties with both NK and T cells. However, it remains unknown whether TIGIT is expressed in CIK cells. Here, we show that TIGIT is expressed by CIK cells and interacts with CD155. By blocking TIGIT using an anti-TIGIT functional antibody, we demonstrate that CIK cells display increased proliferation; higher cytotoxic targeting of tumor cells expressing CD155; and higher expression of interferon-γ (IFN-γ), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α). Furthermore, increases in IFN-γ and cytotoxicity by blockade of TIGIT were reduced by blocking DNAX accessory molecule-1 (DNAM-1) signaling, implying that TIGIT exerts immunosuppressive effects by competing with DNAM-1 for the same ligand, CD155. Our results provide evidence that blockade of TIGIT may be a novel strategy to improve the cytotoxic activity of CIK cells.

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Title: Immunoreceptor TIGIT inhibits the cytotoxicity of human cytokine-induced killer cells by interacting with CD155
Publication date: 01-03-2016
Published in: Cancer Immunology, Immunotherapy / Issue 3/2016
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-016-1799-4

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