New Insights Into the Role of Qa-2 and HLA-G Non-classical MHC-I Complexes in Malignancy

Silva, Istéfani Luciene da; Ferreira, Ênio; Quintanilla, Miguel

doi:10.3389/fimmu.2018.02894

Cited by 25 publications

(16 citation statements)

References 67 publications

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“… 38–43 Some of the immunosuppressive roles described for these TFs include the promotion of exhausted and senescent CD8+ T cells during chronic viral infections by PRDM1, cancer-chemoresistance by the upregulation of regulatory T-cell recruitment through CEBPB, and the induction of T helper cell differentiation toward immunosuppressive Th2 cells by IRF2. 38–41 , 44 , 45 Specific pathways modulated by these TFs in relation to MR1 not yet understood.…”

Section: Discussionmentioning

confidence: 99%

MR1 overexpression correlates with poor clinical prognosis in glioma patients

Kubica

Lara-Velazquez

Bam

et al. 2021

Neuro-Oncology Advances

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Background Glioblastoma is the most common adult primary brain tumor with near universal fatality. Major histocompatibility complex (MHC) class-I molecules are important mediators of CD8 activation and can be downregulated by cancer cells to escape immune surveillance. MR1 is a non-classical MHC-I like molecule responsible for the activation of a subset of T cells. Although high levels of MR1 expression should enhance cancer cell recognition, various tumors demonstrate MR1 overexpression with unknown implications. Here, we study the role of MR1 in glioma. Methods Using multi-omics data from TCGA, we studied MR1 expression patterns and its impact on survival for various solid tumors. In glioma specifically, we validated MR1 expression by histology, elucidate transcriptomic profiles of MR1 high vs low gliomas. To understand MR1 expression we analyzed methylation status of the MR1 gene, and MR1 gene related transcription factor expression. Results MR1 is overexpressed in all grades of glioma and many other solid cancers. However, only in glioma, MR1 overexpression correlated with poor overall survival and demonstrated global dysregulation of many immune related genes in an MR1-dependent manner. MR1 overexpression correlated with decreased MR1 gene methylation and upregulation of predicted MR1 promoter binding TFs, implying MR1 gene methylation might regulate MR1 expression in glioma. Conclusion Our in-silico analysis show that MR1 expression is a predictor of clinical outcome in glioma patients and is potentially regulated at the epigenetic level, resulting in immune related genes dysregulation. These findings need to be validated using independent in vitro and in vivo functional studies.

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Section: Discussionmentioning

confidence: 99%

MR1 overexpression correlates with poor clinical prognosis in glioma patients

Kubica

Lara-Velazquez

Bam

et al. 2021

Neuro-Oncology Advances

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“…It should be noted that cancers can also evade immune elimination by expressing "non-classical" MHC class Ib molecules, HLA-E and HLA-G (26)(27)(28). However, since this immune evasion mechanism is not due to a loss of antigen presentation by "classical" MHC class Ia molecules, but rather through engagement of inhibitory receptors on T lymphocytes and other immune cells (26)(27)(28), this subject is not covered in this review, except as it relates to how MHC I low cancers may evade NK cell recognition. Similarly, MHC II molecules can play a role in cancer immunity, however, since MHC I and MHC II antigen presentation are separate and non-intersecting pathways, this review does not cover the MHC II pathway in cancer.…”

Section: Introductionmentioning

confidence: 99%

Cancer Immune Evasion Through Loss of MHC Class I Antigen Presentation

2021

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Major histocompatibility class I (MHC I) molecules bind peptides derived from a cell's expressed genes and then transport and display this antigenic information on the cell surface. This allows CD8 T cells to identify pathological cells that are synthesizing abnormal proteins, such as cancers that are expressing mutated proteins. In order for many cancers to arise and progress, they need to evolve mechanisms to avoid elimination by CD8 T cells. MHC I molecules are not essential for cell survival and therefore one mechanism by which cancers can evade immune control is by losing MHC I antigen presentation machinery (APM). Not only will this impair the ability of natural immune responses to control cancers, but also frustrate immunotherapies that work by re-invigorating anti-tumor CD8 T cells, such as checkpoint blockade. Here we review the evidence that loss of MHC I antigen presentation is a frequent occurrence in many cancers. We discuss new insights into some common underlying mechanisms through which some cancers inactivate the MHC I pathway and consider some possible strategies to overcome this limitation in ways that could restore immune control of tumors and improve immunotherapy.

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“…However, other studies had found no evidence of functional interaction between sHLA-G and KIR2DL4 in NK cells [ 35 ]. Therefore, whether HLA-G/KIR2DL4 interaction affects the activity of NK cells remains controversial [ 36 ].…”

Section: Hla-g Mediates Immune Regulationmentioning

confidence: 99%

Immunomodulating functions of human leukocyte antigen-G and its role in graft-versus-host disease after allogeneic hematopoietic stem cell transplantation

Zhong

et al. 2021

Ann Hematol

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Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative therapeutic strategy to treat several hematological malignancies and non-hematological malignancies. However, graft-versus-host disease (GVHD) is a frequent and serious transplant-related complication which dramatically restrains the curative effect of allo-HSCT and a significant cause of morbidity and mortality in allogeneic HCT recipients. Effective prevention of GVHD mainly depends on the induction of peripheral immune tolerance. Human leukocyte antigen-G (HLA-G) is a non-classical MHC class I molecule with a strong immunosuppressive function, which plays a prominent role in immune tolerance. HLA-G triggers different reactions depending on the activation state of the immune cells and system. It also exerts a long-term immune tolerance mechanism by inducing regulatory cells. In this present review, we demonstrate the immunomodulatory properties of human leukocyte antigen-G and highlight the role of HLA-G as an immune regulator of GVHD. Furthermore, HLA-G could also serve as a good predictor of GVHD and represent a new therapeutic target for GVHD.

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New Insights Into the Role of Qa-2 and HLA-G Non-classical MHC-I Complexes in Malignancy

Cited by 25 publications

References 67 publications

MR1 overexpression correlates with poor clinical prognosis in glioma patients

MR1 overexpression correlates with poor clinical prognosis in glioma patients

Cancer Immune Evasion Through Loss of MHC Class I Antigen Presentation

Immunomodulating functions of human leukocyte antigen-G and its role in graft-versus-host disease after allogeneic hematopoietic stem cell transplantation

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