Altered phenotypic and functional characteristics of CD3+CD56+ NKT-like cells in human gastric cancer
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Liu-sheng Peng1, Fang-yuan Mao1, Yong-liang Zhao2, Ting-ting Wang1, Na Chen1, Jin-yu Zhang1, Ping Cheng1, Wen-hua Li1, Yi-pin Lv1, Yong-sheng Teng1, Gang Guo1, Ping Luo1, Weisan Chen3, Quan-ming Zou1, Yuan Zhuang1
1National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Third Military Medical University, Chongqing, PR China
2Department of General Surgery and Center of Minimal Invasive Gastrointestinal Surgery, Southwest Hospital, Third Military Medical University, Chongqing, PR China
3La Trobe Institute for Molecular Science, La Trobe University, Bundoora, Victoria, Australia
Yuan Zhuang, email: [email protected]
Quan-ming Zou, email: [email protected]
Keywords: NKT-like cells, gastric cancer, functional impairment, tumor progression, immune escape
Received: December 08, 2015 Accepted: May 28, 2016 Published: July 08, 2016
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.
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