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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-?, TNF-?, 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.

SUBMITTER: Peng LS

PROVIDER: S-EPMC5342413 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature

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

Peng Liu-Sheng LS Mao Fang-Yuan FY Zhao Yong-Liang YL Wang Ting-Ting TT Chen Na N Zhang Jin-Yu JY Cheng Ping P Li Wen-Hua WH Lv Yi-Pin YP Teng Yong-Sheng YS Guo Gang G Luo Ping P Chen Weisan W Zou Quan-Ming QM Zhuang Yuan Y

Oncotarget 20160801 34

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 cell ...[more]

PMID: 27409423

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Project description:BackgroundIn children undergoing chemotherapy yearly influenza vaccination is recommended by treatment protocols. We investigated the relationship between cellular immunity and the antibody response to inactivated influenza vaccines.Methods25 patients (age: 2-18 years) undergoing chemotherapy for different malignancies participated in our study. Flow cytometric detection of peripheral blood lymphocyte subpopulations together with hemagglutination inhibition antibody titers were measured before and 21-28 days after vaccination. We examined the ratio and total numbers of CD3+, CD4+, CD8+ T cells, activated helper (CD3+CD4+CD25low), regulatory (CD3+CD4+CD25high), naive (CD3+CD45RA+) and memory (CD3+CD45RO+) T cells, CD56+NK, and CD3+CD56+ (NKT-like) cells. Relationships between specific antibody responses (seroprotection, seroconversion, geometric mean titer (GMT), geometric mean fold increase (GMFI)) and the ratios and counts of lymphocyte subpopulations were evaluated using one-way ANOVA and the paired sample t test after dichotomization according to age-related reference values.ResultsPatients with CD4+ lymphocyte levels in the normal age-specific range showed significantly better response regarding postvaccination GMT elevation for H1N1 and H3N2 strains (97.52 vs. 19.2, p=0.019, 80 vs. 14.43, p=0.021, respectively). GMFI results were significant only against B strain (2.69-fold vs. 1.23-fold, p=0.046). Prevaccination CD3+CD56+ (NKT-like) cells above predicted values according to age showed significant associations both in postvaccination GMT elevation (H1N1: 75.11 vs. 14.14, p=0.010; H3N2: 62.18 vs. 11.22, p=0.012; B: 22.69 vs. 6.67, p=0.043) and GMFI against all three strains (H1N1: 3.76-fold vs. 1.06-fold, p=0.015; H3N2: 2.74-fold vs. 1, p=0.013; B: 2.57-fold vs. 1, p=0.008). By one-way ANOVA, we found a positive relation between absolute lymphocyte cell count above 1000/µl and the postvaccination GMT elevation against H3N2 (12.81 vs. 56.56, p=0.032), and GMFI regarding H1N1 (1.22-fold vs. 3.48-fold, p=0.044).ConclusionsIn addition to verifying the predictive value of absolute lymphocyte count above 1000/µl, our results suggest an association between NKT-like cell counts and the specific antibody response against all three investigated influenza strains in highly immunosuppressed patients. Furthermore, prevaccination CD4+ lymphocyte levels in the normal age-specific range may influence seroresponse.

Project description:TIGIT expression on natural killer (NK) cells is associated with dysfunction during chronic HIV infection, but the phenotype and biological functions of these cells in the context of acute HIV-1 infection remain poorly understood. Here, 19 acutely infected HIV-1 patients traced at first, third and twelfth month, and age-matched patients with chronic HIV-1 infection were enrolled to investigate the phenotype and functions of TIGIT expression on NK cells. We found that TIGIT-expressing NK cells did not increase in frequency in the first, third and twelfth month of infection until chronic HIV-1 infection lasted over 2 years. The number of TIGIT+NK cells in acute infection was positively associated with HIV-1 viral load (r = 0.53, P = 0.0009). CD96 was significantly upregulated on NK cells after acute infection for 1 month and in chronic infection over 2 years, while CD226 was downregulated in chronic infection over 2 years. Further, at different stages of infection, CD96-CD226+ cells diminished among total NK cells, TIGIT+NK and TIGIT-NK cells, while CD96+CD226- cells expanded. Reduced CD96-CD226+ cells and elevated CD96+CD226- cells among NK cells especially TIGIT-NK cells, had opposite associations with viral load in the first month of infection, as well as CD4 T-cell counts in including the twelfth month and more than 2 years of chronic infection. In both HIV-1-infected individuals and healthy donors, TIGIT was predominantly expressed in NKG2A-NKG2C+NK cells, with a significantly higher proportion than in NKG2A+NKG2C-NK cells. Moreover, the frequencies of TIGIT+NK cells were positively associated with the frequencies of NKG2A-NKG2C+NK cells in acute infection (r = 0.62, P < 0.0001), chronic infection (r = 0.37, P = 0.023) and healthy donors (r = 0.36, P = 0.020). Enhanced early activation and coexpression of CD38 and HLA-DR in TIGIT+NK cells were detected compared to TIGIT-NK cells, both of which were inversely associated with the decrease in CD4 T-cell counts in both acute and chronic HIV-1 infection. The ability of TIGIT+NK cells to produce TNF-α, IFN-γ and CD107a degranulation substance were consistently weaker than that of TIGIT-NK cells in both acute and chronic infection. Moreover, the functionalities of TIGIT+NK cells were lower than those of TIGIT-NK cells, except for TNF-α-CD107a+IFN-γ-NK cells. These findings highlight the phenotype and functional characteristics of TIGIT-expressing NK cells which have poor capabilities in inhibiting HIV-1 replication and maintaining CD4 T-cell counts.

Dataset Information

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

Publications

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

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