Natural killer cell exhaustion in lung cancer

Li, Qi; Cai, Suna; Li, Mengjiao; Zhou, Xiaojie; Wu, Gao; Kang, Kang; Yuan, Jingli; Wang, Ruohan; Huyan, Ting; Zhang, Wei

doi:10.1016/j.intimp.2021.107764

Cited by 8 publications

(7 citation statements)

References 40 publications

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“…CD226 (also known as DNAX Accessory Molecule-1, DNAM-1, PTA-1, and TLiSA1) is a surface receptor that is expressed on some types of immune cells, such as T cells, NK cells, B cells and monocytes, which has been shown to be required for cancer immunosurveillance [8]. The upregulated expression of NKG2A and downregulated level of CD226 were observed in the lung cancer group compared with the control group in a previous study [9]. Recent studies have shown the promotive role of NK cells in various cancers, including prostate cancer, colon cancer and NSCLC [10,11].…”

Section: Introductionmentioning

confidence: 91%

miR-150-5p-Containing Extracellular Vesicles Are a New Immunoregulator That Favor the Progression of Lung Cancer in Hypoxic Microenvironments by Altering the Phenotype of NK Cells

Chang

Tsai

Hung

et al. 2021

Cancers

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Natural killer (NKs) cells are cytotoxic effector cells, which can modulate tumor metastasis according to their function; however, the role of NK cells in lung cancer has not been extensively investigated. In this study, we determined the functional profiles of NK cells in a hypoxic tumor microenvironment (TME) of lung cancer. We revealed CD226 downregulation and functional repression of NK cells after hypoxic lung cancer priming and we then investigated their interaction with extracellular vesicles (EVs) and miR-150-5p. We also found that NK cells from lung cancer patients had lower expression of CD226 on their surface and exhibited a pro-inflammatory, pro-angiogenic and tumorigenesis phenotype by expressing VEGF, CXCL1, CXCL8, S100A8 and MMPs. Moreover, inhibition of miR-150 improved tumor surveillance by reversing CD226 expression and subsequently reinstating cytotoxic NK cell activity in an animal model. Our study introduces a new scenario for the pro-inflammatory and pro-angiogenic activities of NK cells in the hypoxic TME in lung cancer.

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Section: Introductionmentioning

confidence: 91%

miR-150-5p-Containing Extracellular Vesicles Are a New Immunoregulator That Favor the Progression of Lung Cancer in Hypoxic Microenvironments by Altering the Phenotype of NK Cells

Chang

Tsai

Hung

et al. 2021

Cancers

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“…For example, the expression level of NKG2A is increased in cancer patients and patients with chronic viral infections, indirectly indicating the potential of NKG2A as a cancer therapeutic target [70,71]. NKG2A is highly expressed in lymphocytes in different tumor microenvironments [72,73]. For instance, NKG2A is overexpressed in human cervical cancer cells, and this mechanism is dependent on interleukin -15 (IL-15) to upregulate its expression in CD8 + T cells, thus inhibiting the cytotoxicity of lymphocytes and rendering them ineffective in killing tumors [74].…”

Section: Nkg2amentioning

confidence: 99%

Dimerization of Transmembrane Proteins in Cancer Immunotherapy

2023

Membranes

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Transmembrane proteins (TMEMs) are integrated membrane proteins that span the entire lipid bilayer and are permanently anchored to it. TMEMs participate in various cellular processes. Some TMEMs usually exist and perform their physiological functions as dimers rather than monomers. TMEM dimerization is associated with various physiological functions, such as the regulation of enzyme activity, signal transduction, and cancer immunotherapy. In this review, we focus on the dimerization of transmembrane proteins in cancer immunotherapy. This review is divided into three parts. First, the structures and functions of several TMEMs related to tumor immunity are introduced. Second, the characteristics and functions of several typical TMEM dimerization processes are analyzed. Finally, the application of the regulation of TMEM dimerization in cancer immunotherapy is introduced.

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“…Since overexpressed HLA-E functions to inhibit the cytotoxicity of cytotoxic lymphocytes, the blockade of NKG2A-HLA-E axis may possibly enhance the cell-based immunotherapeutic efficacy. In addition, according to multiple studies, NKG2A is also overexpressed in tumor-infiltrating cytotoxic lymphocytes in many types of tumors ( 55 , 66 , 75 ). The increase in the number of NKG2A + tumor infiltrating lymphocytes (TILs) is correlated with a poor prognosis in patients undergoing colorectal, ovary and liver cancer ( 65 , 72 ).…”

Section: The Functions Of Nkg2a In Immunopathological Settingsmentioning

confidence: 99%

Implications of NKG2A in immunity and immune-mediated diseases

2022

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In recent studies, NKG2A is revealed to be a key immune checkpoint for both natural killer (NK) cells and CD8+ T cells. It form heterodimer receptors with CD94, and targets the peptide-presenting human leukocyte antigen-E (HLA-E) molecules. Upon crosslinking, NKG2A/CD94 delivers inhibitory signals for NK cells and CD8+ T cells, while blocking NKG2A can effectively unleash functions of these cytotoxic lymphocytes. The interaction between NKG2A and HLA-E contributes to tumor immune escape, and NKG2A-mediated mechanisms are currently being exploited to develop potential antitumor therapeutic strategies. In addition, growing evidence shows that NKG2A also plays important roles in other immune-related diseases including viral infections, autoimmune diseases, inflammatory diseases, parasite infections and transplant rejection. Therefore, the current work focuses on describing the effect of NKG2A on immune regulation and exploring its potential role in immune-mediated disorders.

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Natural killer cell exhaustion in lung cancer

Cited by 8 publications

References 40 publications

miR-150-5p-Containing Extracellular Vesicles Are a New Immunoregulator That Favor the Progression of Lung Cancer in Hypoxic Microenvironments by Altering the Phenotype of NK Cells

miR-150-5p-Containing Extracellular Vesicles Are a New Immunoregulator That Favor the Progression of Lung Cancer in Hypoxic Microenvironments by Altering the Phenotype of NK Cells

Dimerization of Transmembrane Proteins in Cancer Immunotherapy

Implications of NKG2A in immunity and immune-mediated diseases

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