Altered phenotypic and functional characteristics of CD3+CD56+ NKT-like cells in human gastric cancer

// Liu-sheng Peng 1 , Fang-yuan Mao 1 , Yong-liang Zhao 2 , Ting-ting Wang 1 , Na Chen 1 , Jin-yu Zhang 1 , Ping Cheng 1 , Wen-hua Li 1 , Yi-pin Lv 1 , Yong-sheng Teng 1 , Gang Guo 1 , Ping Luo 1 , Weisan Chen 3 , Quan-ming Zou 1 , Yuan Zhuang 1 1 National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Third Military Medical University, Chongqing, PR China 2 Department of General Surgery and Center of Minimal Invasive Gastrointestinal Surgery, Southwest Hospital, Third Military Medical University, Chongqing, PR China 3 La Trobe Institute for Molecular Science, La Trobe University, Bundoora, Victoria, Australia Correspondence to: Yuan Zhuang, email: yuanzhuang1983@yahoo.com Quan-ming Zou, email: qmzou@tmmu.edu.cn Keywords: NKT-like cells, gastric cancer, functional impairment, tumor progression, immune escape Received: December 08, 2015     Accepted: May 28, 2016     Published: July 08, 2016 ABSTRACT CD3 + CD56 + natural killer T (NKT)-like cells are a group of CD3 + T cells sharing characteristics of NK and T cells and constitute a major component of host anti-tumor immune response in human cancer. However, the nature, function and clinical relevance of CD3 + CD56 + NKT-like cells in human gastric cancer (GC) remain unclear. In this study, we showed that the frequencies of CD3 + CD56 + NKT-like cells in GC tumors were significantly decreased and low levels of tumor-infiltrating CD3 + CD56 + NKT-like cells were positively correlated with poor survival and disease progression. Most CD3 + CD56 + NKT-like cells in GC tumors were CD45RA - CD27 +/- central/effector-memory cells with decreased activity and lower expression levels of CD69, NKG2D and DNAM-1 than those in non-tumor tissues. We further observed that tumor-infiltrating CD3 + CD56 + NKT-like cells had impaired effector function as shown by decreased IFN-γ, TNF-α, granzyme B and Ki-67 expression. Moreover, in vitro studies showed that soluble factors released from GC tumors could induce the functional impairment of CD3 + CD56 + NKT-like cells. Collectively, our data indicate that decreased tumor-infiltrating CD3 + CD56 + NKT-like cells with impaired effector function are associated with tumor progression and poor survival of GC patients, which may contribute to immune escape of GC.