A different representation of natural T cells and natural killer cells between tumor-infiltrating and periphery lymphocytes in human hepatocellular carcinoma

Li, Xiaofeng; Dong, Diansheng; Song, Xiaomin; Liu, Jianjing; Zhu, Lihong; Zhu, Xiaodong; Ma, Wenchao; Xu, Wengui

doi:10.3892/ol.2017.5808

Cited by 10 publications

(11 citation statements)

References 45 publications

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“…After resection of the primary tumor, type I NKT cell numbers did not increase in patients with different cancer types ( 213 , 220 ). By contrast, circulating NKT-like cell numbers were not decreased in patients diagnosed with laryngeal cancer, gastric cancer, or hepatocellular carcinoma ( 91 , 92 , 220 ).…”

Section: The Function and Phenotype Of Nkt Cells In Patients Diagnosementioning

confidence: 90%

“…In addition, it was observed that type I NKT cell infiltration in neuroblastomas was associated with CCL2 expression on tumor cells, indicating that expression of homing receptors on tumors was essential for infiltration of type I NKT cells in neuroblastoma ( 212 ). Furthermore, in two studies ( 91 , 92 ) the function and phenotype of infiltrating NKT-like cells in tumors were described. Peng et al reported impaired effector function of infiltrating NKT-like cells in gastric cancer-derived tumor tissue compared with non-tumor tissue, characterized by decreased expression of IFN-γ, TNF-α, granzyme B, and Ki-67 ( 91 ).…”

Section: The Function and Phenotype Of Nkt Cells In Patients Diagnosementioning

confidence: 99%

“…Furthermore, this study also showed decreased expression of the lymphocyte proliferation marker CD69, the homing receptors CXCR3 and CCR5, and the NKRs NKG2D and DNAM-1 on NKT-like cells in tumor tissue compared with non-tumor tissue. In addition, a study on patients with hepatocellular carcinoma showed that NKT-like cells in tumor tissue expressed FOXP3 and lost expression of IFN-γ and perforin compared with NKT-like cells in non-tumor tissue ( 92 ).…”

Section: The Function and Phenotype Of Nkt Cells In Patients Diagnosementioning

confidence: 99%

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The Role of Natural Killer T Cells in Cancer—A Phenotypical and Functional Approach

2018

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Natural killer T (NKT) cells are a subset of CD1d-restricted T cells at the interface between the innate and adaptive immune system. NKT cells can be subdivided into functional subsets that respond rapidly to a wide variety of glycolipids and stress-related proteins using T- or natural killer (NK) cell-like effector mechanisms. Because of their major modulating effects on immune responses via secretion of cytokines, NKT cells are also considered important players in tumor immunosurveillance. During early tumor development, T helper (TH)1-like NKT cell subsets have the potential to rapidly stimulate tumor-specific T cells and effector NK cells that can eliminate tumor cells. In case of tumor progression, NKT cells may become overstimulated and anergic leading to deletion of a part of the NKT cell population in patients via activation-induced cell death. In addition, the remaining NKT cells become hyporesponsive, or switch to immunosuppressive TH2-/T regulatory-like NKT cell subsets, thereby facilitating tumor progression and immune escape. In this review, we discuss this important role of NKT cells in tumor development and we conclude that there should be three important focuses of future research in cancer patients in relation with NKT cells: (1) expansion of the NKT cell population, (2) prevention and breaking of NKT cell anergy, and (3) skewing of NKT cells toward TH1-like subsets with antitumor activity.

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Section: The Function and Phenotype Of Nkt Cells In Patients Diagnosementioning

confidence: 90%

Section: The Function and Phenotype Of Nkt Cells In Patients Diagnosementioning

confidence: 99%

Section: The Function and Phenotype Of Nkt Cells In Patients Diagnosementioning

confidence: 99%

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The Role of Natural Killer T Cells in Cancer—A Phenotypical and Functional Approach

2018

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“…The mature perforin molecule is composed of 534 amino acid residues with a molecular weight of 56-75 kDa and an isoelectric point (IP) of 6.4 [84]. Li et al [85] observed the differential expression of NK cells in tumorous tissue infiltrating lymphocytes (TILs) and non-tumorous tissue infiltrating lymphocytes (NILs) and PBMCs of patients with HCC by multicolor fluorescence activated cell classification analysis. It was found that NK cells in TILs and NILs were only 6.324 ± 1.559 and 14.52 ± 2.336, respectively.…”

Section: Perforin Secreted By Nk Cells Exerts Anti-hepatocarcinoma Acmentioning

confidence: 99%

Recent Advances in Molecular Mechanisms of the NKG2D Pathway in Hepatocellular Carcinoma

Wang¹,

Li²,

Sun³

2020

Biomolecules

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Hepatocellular carcinoma is a common malignant tumor with high mortality. Its malignant proliferation, invasion, and metastasis are closely related to the cellular immune function of the patients. NKG2D is a key activated and type II membrane protein molecule expressed on the surface of almost all NK cells. The human NKG2D gene is 270 kb long, located at 12p12.3–p13.1, and contains 10 exons and 9 introns. The three-dimensional structure of the NKG2D monomeric protein contains two alpha-helices, two beta-lamellae, and four disulfide bonds, and its’ signal of activation is transmitted mainly by the adaptor protein (DAP). NKG2D ligands, including MICA, MICB, and ULBPs, can be widely expressed in hepatoma cells. After a combination of NKG2D and DAP10 in the form of homologous two polymers, the YxxM motif in the cytoplasm is phosphorylated and then signaling pathways are also gradually activated, such as PI3K, PLCγ2, JNK-cJunN, and others. Activated NK cells can enhance the sensitivity to hepatoma cells and specifically dissolve by releasing a variety of cytokines (TNF-α and IFN-γ), perforin, and high expression of FasL, CD16, and TRAIL. NK cells may specifically bind to the over-expressed MICA, MICB, and ULBPs of hepatocellular carcinoma cells through the surface activating receptor NKG2D, which can help to accurately identify hepatoma, play a critical role in anti-hepatoma via the pathway of cytotoxic effects, and obviously delay the poor progress of hepatocellular carcinoma.

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“…Due to a lack of specific markers, it is not possible as yet to identify the entire NKT cell population using flow cytometry or immunohistochemistry [ 25 ]. In many studies, co-expression of CD3 and CD56 is used to identify NKT cells [ 26 – 31 ]. Although it is likely that the CD3 + CD56 + cell population includes “true” CD1d-restricted NKT cells, it has to be taken into account that conventional T cells have also been reported to express CD56 [ 32 , 33 ].…”

Section: Introductionmentioning

confidence: 99%

Characterization of circulating T-, NK-, and NKT cell subsets in patients with colorectal cancer: the peripheral blood immune cell profile

Krijgsman

Vries

Skovbo

et al. 2019

Cancer Immunol Immunother

122

113

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Objective As the development and progression of colorectal cancer (CRC) are known to be affected by the immune system, cell subsets such as T cells, natural killer (NK) cells, and natural killer T (NKT) cells are considered interesting targets for immunotherapy and clinical biomarker research. Until now, the role of systemic immune profiles in tumor progression remains unclear. In this study, we aimed to characterize the immunophenotype of circulating T cells, NK cells, and NKT-like cells in patients with CRC, and to subsequently correlate these immunophenotypes to clinical follow-up data. Methods Using multiparameter flow cytometry, the subset distribution and immunophenotype of T cells (CD3 + CD56 − ), CD56 dim NK cells (CD3 − CD56 dim ), CD56 bright NK cells (CD3 − CD56 bright ), and NKT-like (CD3 + CD56 + ) cells were investigated in peripheral blood mononuclear cell (PBMC) samples from 71 CRC patients and 19 healthy donors. Results CRC patients showed profound differences in immune cell subset distribution and their immunophenotype compared to healthy donors, as characterized by increased percentage of regulatory T cells, and reduced expression level of the natural cytotoxicity receptors NKp44 and NKp46 on both CD56 dim NK cells and NKT-like cells. Finally, we showed in a multivariate analysis that above-median percentage of CD16 + NKT-like cells was independently associated with shorter disease-free survival in CRC patients. Conclusion The altered phenotype of circulating immune cell subsets in CRC and its association with clinical outcome highlight the potential use of PBMC subsets as prognostic biomarkers in CRC, thereby contributing to better insight into the role of systemic immune profiles in tumor progression. Electronic supplementary material The online version of this article (10.1007/s00262-019-02343-7) contains supplementary material, which is available to authorized users.

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A different representation of natural T cells and natural killer cells between tumor-infiltrating and periphery lymphocytes in human hepatocellular carcinoma

Cited by 10 publications

References 45 publications

The Role of Natural Killer T Cells in Cancer—A Phenotypical and Functional Approach

The Role of Natural Killer T Cells in Cancer—A Phenotypical and Functional Approach

Recent Advances in Molecular Mechanisms of the NKG2D Pathway in Hepatocellular Carcinoma

Characterization of circulating T-, NK-, and NKT cell subsets in patients with colorectal cancer: the peripheral blood immune cell profile

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