Inhibiting HLA-G restores IFN-γ and TNF-α producing T cell in pleural Tuberculosis

Saurabh, Abhinav; Chakraborty, Sushmita; Kumar, Prabin; Bhatnagar, Anuj; Rishi, Narayan

doi:10.1016/j.tube.2018.01.008

Cited by 11 publications

(11 citation statements)

References 25 publications

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“…There is accumulating evidence suggesting the significance of HLA-G mediated TNF-α regulation 53–55. Furthermore, earlier findings on association of TNF-α polymorphisms with various class I and II HLA alleles56 impelled us to assess the effect of extended haplotypes and SNP-SNP interaction of TNF-α and HLA-G in breast cancer.…”

Section: Discussionmentioning

confidence: 99%

Association ofHLA-G3'UTR 14-bp Ins/Del polymorphism with breast cancer among South Indian women

et al. 2019

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AimHuman leucocyte antigen-G (HLA-G) and tumour necrosis factor-alpha (TNF-α) are potent immune mediators implicated in the pathogenesis of breast cancer. The polymorphisms in the 3' untranslated region (3'UTR) of HLA-G and promoter region of TNF-α are well known to influence their expression levels and may consequently contribute to varied disease predisposition. Therefore, in the present study, we explored the effect of HLA-G 3'UTR (14-bp Ins/Del and +3142 C/G) and TNF-α promoter (–238 G/A and –308 G/A) polymorphisms on breast cancer risk among South Indian women.MethodsA total of 342 women (100 patients with breast cancer, 142 patients with benign breast disorder and 100 healthy women volunteers) were enrolled for this study. Genotyping of HLA-G and TNF-α polymorphisms were performed by direct PCR DNA amplification and amplification refractory mutation system PCR methods, respectively.ResultsSignificantly higher frequencies of HLA-G 14-bp Ins allele and Ins/+3142G haplotype were observed in patients with breast cancer than healthy controls (OR=1.56, Pc=0.036) and patients with benign breast disorder (OR=1.47, Pc=0.046). Similarly, subgroup analysis based on age at diagnosis (age≤50 years and >50 years) of breast cancer revealed higher frequencies of 14-bp Ins allele and Ins/+3142G haplotype in the patients of age >50 years than healthy controls (OR=1.77, Pc=0.03). Additionally, the extended haplotypes and multifactor dimensionality reduction analysis of the studied polymorphisms revealed significant contribution of HLA-G 14-bp Ins/Del polymorphism towards breast cancer risk.ConclusionThe findings of the present study suggest that the HLA-G 14-bp Ins/Del polymorphism could influence breast cancer pathogenesis among South Indian women.

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Section: Discussionmentioning

confidence: 99%

Association ofHLA-G3'UTR 14-bp Ins/Del polymorphism with breast cancer among South Indian women

et al. 2019

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“…HIF‐1 controls HLA‐G transcription through HLA‐G HRE, which contains specific binding sites for HIF‐1. IFN‐γ and tumor necrosis factor‐α (TNF‐α) are suppressed by HLA‐G, leading to nondestructive and detectable tumors associated with NK and T cells 36,76 . HLA‐G mediated immunosuppressive effect by binding to immunoglobulin‐like transcript‐2, which is expressed on immune cells, such as B and T cells, in tuberculosis pleural effusion patients 76 .…”

Section: Effect Of Hif‐1 On Immune Checkpoint Moleculesmentioning

confidence: 99%

“…IFN‐γ and tumor necrosis factor‐α (TNF‐α) are suppressed by HLA‐G, leading to nondestructive and detectable tumors associated with NK and T cells 36,76 . HLA‐G mediated immunosuppressive effect by binding to immunoglobulin‐like transcript‐2, which is expressed on immune cells, such as B and T cells, in tuberculosis pleural effusion patients 76 . The HLA‐G antigen was expressed in some tumor tissues 36 and was found to impede the body's immune response by inhibiting the effects of NK cells and cytotoxic T lymphocytes, changing the mode of cytokine secretion and thereby enabling tumor cells to escape from the immune response, survive, and develop 36,76 .…”

Section: Effect Of Hif‐1 On Immune Checkpoint Moleculesmentioning

confidence: 99%

“…HLA‐G mediated immunosuppressive effect by binding to immunoglobulin‐like transcript‐2, which is expressed on immune cells, such as B and T cells, in tuberculosis pleural effusion patients 76 . The HLA‐G antigen was expressed in some tumor tissues 36 and was found to impede the body's immune response by inhibiting the effects of NK cells and cytotoxic T lymphocytes, changing the mode of cytokine secretion and thereby enabling tumor cells to escape from the immune response, survive, and develop 36,76 . However, it should be noted that the relationship between HLA‐G and tumorigenesis remains to be further clarified.…”

Section: Effect Of Hif‐1 On Immune Checkpoint Moleculesmentioning

confidence: 99%

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The role of hypoxia‐inducible factor 1 in tumor immune evasion

Wang

et al. 2020

Medicinal Research Reviews

181

136

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Hypoxia‐inducible factor 1 (HIF‐1) plays an indispensable role in the hypoxic tumor microenvironment. Hypoxia and HIF‐1 are involved in multiple aspects of tumor progression, such as metastasis, angiogenesis, and immune evasion. In innate and adaptive immune systems, malignant tumor cells avoid their recognition and destruction by HIF‐1. Tumor immune evasion allows cancer cells to proliferate and metastasize and is associated with immunotherapy failure and chemoresistance. In the hypoxic tumor microenvironment, HIF‐1 signaling suppresses the innate and adaptive immune systems to evade immune attack by inducing the expression of immunosuppressive factors and immune checkpoint molecules, including vascular endothelial growth factor, prostaglandin E2, and programmed death‐ligand 1/programmed death‐1. Moreover, HIF‐1 blocks tumor‐associated antigen presentation via major histocompatibility complex class I chain‐related/natural killer group 2, member D signaling. Tumor‐associated autophagy and the release of tumor‐derived exosomes contribute to HIF‐1‐mediated immune evasion. This review focuses on recent findings on the potential mechanism(s) underlying the effect of hypoxia and HIF‐1 signaling on tumor immune evasion in the hypoxic tumor microenvironment. The effects of HIF‐1 on immune checkpoint molecules, immunosuppressive molecules, autophagy, and exosomes have been described. Additionally, the potential role of HIF‐1 in the regulation of tumor‐derived exosomes, as well as the roles of HIF‐1 and exosomes in tumor evasion, are discussed. This study will contribute to our understanding of HIF‐1‐mediated tumor immune evasion, leading to the development of effective HIF‐1‐targeting drugs and immunotherapies.

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“…During the past several decades, in addition to its initial discovery on extravillous cytotrophoblasts, the aberrant expression of HLA-G has been observed in many disorders (8). The immune suppressive potential of HLA-G has also been established, and HLA-G can obviously inhibit the functions of immune cells, such as natural killer (NK) cells (9), T cells (10), dendritic cells (DCs) (11), neutrophils, and B cells, through the immune inhibitory receptors immunoglobulin (Ig)-like transcript receptor 2 (ILT2) and/or ILT4, and the HLA-G/ILT signaling pathway, acting as an immune checkpoint, has also been recognized (12–14). HLA-E can affect both innate and adaptive immune responses by interacting with the inhibitory CD94-NKG2A receptor and also with the activating receptor NKG2C on NK cells and the CD8 receptor on T cells (15).…”

Section: Introductionmentioning

confidence: 99%

The Emerging Roles of Human Leukocyte Antigen-F in Immune Modulation and Viral Infection

Lin

Yan

2019

Front. Immunol.

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Human leukocyte antigens (HLAs) play various critical roles in both innate and adaptive immunity through processes such as presenting antigens to T cells and serving as ligands for receptors expressed on natural killer (NK) cells. Among the HLA class I family, the clinical significance and biological function of HLA-F have been the least investigated and have remained elusive for a long period of time. Previous studies have revealed that HLA-F expression might be involved in various physiological and pathological processes, such as pregnancy, viral infection, cancer, transplantation, and autoimmune diseases. However, recent data have shown that, akin to other HLA family members, HLA-F molecules can interact with both activating and inhibitory receptors on immune cells, such as NK cells, and can present a diverse panel of peptides. These important findings pave new avenues for investigations regarding the functions of HLA-F as an important immune regulatory molecule. In the present review, we summarize the studies on the role of HLA-F in immune modulation, with a special emphasis placed on the roles of HLA-F and KIR3DS1 interactions in viral infection.

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Inhibiting HLA-G restores IFN-γ and TNF-α producing T cell in pleural Tuberculosis

Cited by 11 publications

References 25 publications

Association ofHLA-G3'UTR 14-bp Ins/Del polymorphism with breast cancer among South Indian women

Association ofHLA-G3'UTR 14-bp Ins/Del polymorphism with breast cancer among South Indian women

The role of hypoxia‐inducible factor 1 in tumor immune evasion

The Emerging Roles of Human Leukocyte Antigen-F in Immune Modulation and Viral Infection

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