title: Immunoreceptor TIGIT inhibits the cytotoxicity of human cytokine-induced killer cells by interacting with CD155.
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.
authors: Cancer Center, The Affiliated Hospital of Xuzhou Medical College, 89 West Huai-hai Road, Xuzhou, 221006, Jiangsu, China.|Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical College, Xuzhou, 221002, Jiangsu, China.
authors: Baofu
authors: B
authors: Zhang
authors: Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical College, Xuzhou, 221002, Jiangsu, China.
authors: Weina
authors: W
authors: Zhao
authors: Cancer Center, The Affiliated Hospital of Xuzhou Medical College, 89 West Huai-hai Road, Xuzhou, 221006, Jiangsu, China.|Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical College, Xuzhou, 221002, Jiangsu, China.
authors: Huizhong
authors: H
authors: Li
authors: Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical College, Xuzhou, 221002, Jiangsu, China.
authors: Yuanyuan
authors: Y
authors: Chen
authors: Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical College, Xuzhou, 221002, Jiangsu, China.
authors: Hui
authors: H
authors: Tian
authors: Cancer Center, The Affiliated Hospital of Xuzhou Medical College, 89 West Huai-hai Road, Xuzhou, 221006, Jiangsu, China.|Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical College, Xuzhou, 221002, Jiangsu, China.
authors: Liantao
authors: L
authors: Li
authors: Cancer Center, The Affiliated Hospital of Xuzhou Medical College, 89 West Huai-hai Road, Xuzhou, 221006, Jiangsu, China.|Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical College, Xuzhou, 221002, Jiangsu, China.
authors: Longzhen
authors: L
authors: Zhang
authors: Cancer Center, The Affiliated Hospital of Xuzhou Medical College, 89 West Huai-hai Road, Xuzhou, 221006, Jiangsu, China. chg200811@126.com.|Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical College, Xuzhou, 221002, Jiangsu, China. chg200811@126.com.
authors: Chao
authors: C
authors: Gao
authors: Cancer Center, The Affiliated Hospital of Xuzhou Medical College, 89 West Huai-hai Road, Xuzhou, 221006, Jiangsu, China. jnzheng@xzmc.edu.cn.|Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical College, Xuzhou, 221002, Jiangsu, China. jnzheng@xzmc.edu.cn.
authors: Junnian
authors: J
authors: Zheng
mesh_terms: D000945:Antigens, Differentiation, T-Lymphocyte / Q000502:physiology; D045744:Cell Line, Tumor; D055612:Cytokine-Induced Killer Cells / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D006801:Humans; D011971:Receptors, Immunologic / Q000502:physiology*; D011991:Receptors, Virus / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D000098862:T Lineage-Specific Activation Antigen 1
chemical_list: D000945:Antigens, Differentiation, T-Lymphocyte; D000098862:T Lineage-Specific Activation Antigen 1; D011971:Receptors, Immunologic; D011991:Receptors, Virus; C534712:TIGIT protein, human; C066100:poliovirus receptor
keywords: CD155; CIK cells; DNAM-1; Immunotherapy; TIGIT