title: Altered phenotypic and functional characteristics of CD3+CD56+ NKT-like cells in human gastric cancer.
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.
authors.affiliation: National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Third Military Medical University, Chongqing, PR China.
authors.forename: Liu-Sheng
authors.initials: LS
authors.lastname: Peng
authors.affiliation: National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Third Military Medical University, Chongqing, PR China.
authors.forename: Fang-Yuan
authors.initials: FY
authors.lastname: Mao
authors.affiliation: Department of General Surgery and Center of Minimal Invasive Gastrointestinal Surgery, Southwest Hospital, Third Military Medical University, Chongqing, PR China.
authors.forename: Yong-Liang
authors.initials: YL
authors.lastname: Zhao
authors.affiliation: National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Third Military Medical University, Chongqing, PR China.
authors.forename: Ting-Ting
authors.initials: TT
authors.lastname: Wang
authors.affiliation: National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Third Military Medical University, Chongqing, PR China.
authors.forename: Na
authors.initials: N
authors.lastname: Chen
authors.affiliation: National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Third Military Medical University, Chongqing, PR China.
authors.forename: Jin-Yu
authors.initials: JY
authors.lastname: Zhang
authors.affiliation: National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Third Military Medical University, Chongqing, PR China.
authors.forename: Ping
authors.initials: P
authors.lastname: Cheng
authors.affiliation: National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Third Military Medical University, Chongqing, PR China.
authors.forename: Wen-Hua
authors.initials: WH
authors.lastname: Li
authors.affiliation: National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Third Military Medical University, Chongqing, PR China.
authors.forename: Yi-Pin
authors.initials: YP
authors.lastname: Lv
authors.affiliation: National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Third Military Medical University, Chongqing, PR China.
authors.forename: Yong-Sheng
authors.initials: YS
authors.lastname: Teng
authors.affiliation: National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Third Military Medical University, Chongqing, PR China.
authors.forename: Gang
authors.initials: G
authors.lastname: Guo
authors.affiliation: National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Third Military Medical University, Chongqing, PR China.
authors.forename: Ping
authors.initials: P
authors.lastname: Luo
authors.affiliation: La Trobe Institute for Molecular Science, La Trobe University, Bundoora, Victoria, Australia.
authors.forename: Weisan
authors.initials: W
authors.lastname: Chen
authors.affiliation: National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Third Military Medical University, Chongqing, PR China.
authors.forename: Quan-Ming
authors.initials: QM
authors.lastname: Zou
authors.affiliation: National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Third Military Medical University, Chongqing, PR China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhuang
mesh_terms: D017252:CD3 Complex / Q000032:analysis*; D019002:CD56 Antigen / Q000032:analysis*; D006801:Humans; D017493:Leukocyte Common Antigens / Q000032:analysis; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology; D055611:Natural Killer T-Cells / Q000276:immunology*; D010641:Phenotype; D013274:Stomach Neoplasms / Q000276:immunology*; D059016:Tumor Microenvironment; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000032:analysis
chemical_list: D017252:CD3 Complex; D019002:CD56 Antigen; C522918:NCAM1 protein, human; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D017493:Leukocyte Common Antigens
keywords: NKT-like cells; functional impairment; gastric cancer; immune escape; tumor progression