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

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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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Abbreviations

ABB:

1 × annexin-binding buffer

BSA:

Bovine serum albumin

CFSE:

Carboxyfluorescein diacetate succinimidyl ester

CIK:

Cytokine-induced killer

DNAM-1:

DNAX accessory molecule-1

ELISA:

Enzyme-linked immunosorbent assay

IFN-γ:

Interferon-γ

IL-2:

Interleukin-2

IL-6:

Interleukin-6

ITIM:

Immunoreceptor tyrosine-based inhibition motif

MHC:

Major histocompatibility complex

NK:

Natural killer

OKT-3:

Activating monoclonal antibody against CD3

PBMCs:

Peripheral blood mononuclear cells

PVR:

Poliovirus receptor

TIGIT:

T cell Ig and ITIM domain

TNF-α:

Tumor necrosis factor-α

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Acknowledgments

This project was supported by the National Natural Science Foundation of China (No. 81202015), Jiangsu Provincial Special Program of Medical Science (BL2012020), and the Natural Science Foundation of the Jiangsu Province Higher Education Institutions (No. 12KJB320014).

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Authors and Affiliations

  1. Cancer Center, The Affiliated Hospital of Xuzhou Medical College, 89 West Huai-hai Road, Xuzhou, 221006, Jiangsu, China

    Baofu Zhang, Huizhong Li, Liantao Li, Longzhen Zhang, Chao Gao & Junnian Zheng

  2. Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical College, Xuzhou, 221002, Jiangsu, China

    Baofu Zhang, Weina Zhao, Huizhong Li, Yuanyuan Chen, Hui Tian, Liantao Li, Longzhen Zhang, Chao Gao & Junnian Zheng

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  1. Baofu Zhang
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Correspondence to Chao Gao or Junnian Zheng.

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Zhang, B., Zhao, W., Li, H. et al. Immunoreceptor TIGIT inhibits the cytotoxicity of human cytokine-induced killer cells by interacting with CD155. Cancer Immunol Immunother 65, 305–314 (2016). https://doi.org/10.1007/s00262-016-1799-4

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