Beyond the increasing complexity of the immunomodulatory HLA-G molecule

Blood ◽  
2008 ◽  
Vol 111 (10) ◽  
pp. 4862-4870 ◽  
Author(s):  
Edgardo D. Carosella ◽  
Benoit Favier ◽  
Nathalie Rouas-Freiss ◽  
Philippe Moreau ◽  
Joel LeMaoult
Keyword(s):  
Human Leukocyte ◽  
Hematologic Malignancies ◽  
Therapeutic Tool ◽  
Leukocyte Antigen ◽  
Histocompatibility Complex ◽  
Maternal Immune System ◽  
Precise Knowledge ◽  
Mhc Class I Molecule ◽  
Human Leukocyte Antigen G ◽  
Immunomodulatory Function

Abstract Human leukocyte antigen G (HLA-G) is a nonclassic major histocompatibility complex (MHC) class I molecule that functions as an immunomodulatory molecule capable of protecting fetal tissues from the maternal immune system. The relevance of HLA-G in other contexts was investigated soon afterward. Numerous studies have sought (and some have shown) the relevance of HLA-G in pathologic conditions, such as transplantation, autoimmunity, and cancer and hematologic malignancies. One of the main goals of the current research on HLA-G is now to use it in the clinic, either for diagnosis or as a therapeutic tool/target. For this, precise knowledge on the nature and functions of HLA-G is critical. We highlight here what we consider are recent key basic findings on the immunomodulatory function of HLA-G. These strengthen the case for considering HLA-G as clinically relevant.

scholarly journals The HLA-G Immune Checkpoint Plays a Pivotal Role in the Regulation of Immune Response in Autoimmune Diseases

2021 ◽  
Vol 22 (24) ◽  
pp. 13348
Author(s):  
Monika Zaborek-Łyczba ◽  
Jakub Łyczba ◽  
Paulina Mertowska ◽  
Sebastian Mertowski ◽  
Anna Hymos ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Autoimmune Diseases ◽  
Mhc Class I ◽  
Hematologic Malignancies ◽  
Leukocyte Antigen ◽  
Histocompatibility Complex ◽  
Mhc Class I Molecule ◽  
Immunomodulatory Function

The human G-leukocyte antigen (HLA-G) molecule is a non-classical major histocompatibility complex (MHC) class I molecule. The pertinence of HLA-G has been investigated in numerous studies which have sought to elucidate the relevance of HLA-G in pathologic conditions, such as autoimmune diseases, cancers, and hematologic malignancies. One of the main goals of the current research on HLA-G is to use this molecule in clinical practice, either in diagnostics or as a therapeutic target. Since HLA-G antigens are currently considered as immunomodulatory molecules that are involved in reducing inflammatory and immune responses, in this review, we decided to focus on this group of antigens as potential determinants of progression in autoimmune diseases. This article highlights what we consider as recent pivotal findings on the immunomodulatory function of HLA-G, not only to establish the role of HLA-G in the human body, but also to explain how these proteins mediate the immune response.

scholarly journals HLA-G/sHLA-G and HLA-G-Bearing Extracellular Vesicles in Cancers: Potential Role as Biomarkers

2021 ◽  
Vol 12 ◽  
Author(s):  
Peilong Li ◽  
Nan Wang ◽  
Yi Zhang ◽  
Chuanxin Wang ◽  
Lutao Du
Keyword(s):  
Potential Role ◽  
Immune Escape ◽  
De Novo ◽  
Human Leukocyte ◽  
Leukocyte Antigen ◽  
Diagnosis And Prognosis ◽  
Mhc Class I Molecule ◽  
Tumor Environment ◽  
Highly Correlated ◽  
Human Leukocyte Antigen G

As a non-classic major histocompatibility complex (MHC) class I molecule, human leukocyte antigen G (HLA-G) is expressed in fetal-maternal interface and immunoprivileged site only in healthy condition, and in pathological conditions such as cancer, it can be de novo expressed. It is now widely accepted that HLA-G is a key molecule in the process of immune escape of cancer cells, which is ubiquitously expressed in the tumor environment. This raises the possibility that it may play an adverse role in tumor immunity. The expression level of HLA-G has been demonstrated to be highly correlated with clinical parameters in many tumors, and its potential significance in the diagnosis and prognosis of cancer has been postulated. However, because HLA-G itself has up to seven different subtypes, and for some subtypes, detected antibodies are few or absent, it is hard to evaluate the actual expression of HLA-G in tumors. In the present work, we described (a) the structure and three main forms of HLA-G, (b) summarized the mechanism of HLA-G in the immune escape of tumor cells, (c) discussed the potential role of HLA-G as a tumor marker, and reviewed (d) the methods for detecting and quantifying HLA-G.

T Cells: A Growing Universe of Roles in Neurodegenerative Diseases

2021 ◽  
pp. 107385842110249
Author(s):  
Dallin Dressman ◽  
Wassim Elyaman
Keyword(s):  
T Cells ◽  
T Cell ◽  
Neurodegenerative Diseases ◽  
Human Leukocyte ◽  
Autoimmune Response ◽  
Antigen Specificity ◽  
Risk Genes ◽  
Leukocyte Antigen ◽  
Histocompatibility Complex ◽  
The Central Nervous System

T cells play a central role in homeostasis and host defense against infectious diseases. T cell dysregulation can lead to recognizing self-antigens as foreign antigens, causing a detrimental autoimmune response. T cell involvement in multiple sclerosis (MS), long understood to be an autoimmune-mediated neurodegenerative disease, is well characterized. More recently, a role for T cells has also been identified for the neurodegenerative diseases Alzheimer’s disease (AD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS). Interestingly, several alleles and variants of human leukocyte antigen (HLA) genes have been classified as AD and PD risk genes. HLA codes for components of major histocompatibility complex (MHC) class I or class II, both of which are expressed by microglia, the innate immune cells of the central nervous system (CNS). Thus, both microglia and T cells may potentially interact in an antigen-dependent or independent fashion to shape the inflammatory cascade occurring in neurodegenerative diseases. Dissecting the antigen specificity of T cells may lead to new options for disease-modifying treatments in neurodegenerative diseases. Here, we review the current understanding of T cells in neurodegenerative diseases. We summarize the subsets of T cells, their phenotype and potential functions in animal models and in human studies of neurodegenerative diseases.

Expression of human leukocyte antigen-G in systemic lupus erythematosus

2008 ◽  
Vol 69 (1) ◽  
pp. 9-15 ◽  
Author(s):  
Silvia Rosado ◽  
Gema Perez-Chacon ◽  
Susana Mellor-Pita ◽  
Inmaculada Sanchez-Vegazo ◽  
Carmen Bellas-Menendez ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Human Leukocyte Antigen ◽  
Lupus Erythematosus ◽  
Human Leukocyte ◽  
Systemic Lupus ◽  
Leukocyte Antigen ◽  
Human Leukocyte Antigen G

scholarly journals Human Herpesvirus 6A and 6B inhibit in vitro angiogenesis by induction of Human Leukocyte Antigen G

2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Roberta Rizzo ◽  
Maria D’Accolti ◽  
Daria Bortolotti ◽  
Francesca Caccuri ◽  
Arnaldo Caruso ◽  
...  
Keyword(s):  
Human Leukocyte Antigen ◽  
Human Herpesvirus ◽  
Human Leukocyte ◽  
Leukocyte Antigen ◽  
Human Leukocyte Antigen G ◽  
In Vitro Angiogenesis

scholarly journals Targeting human leukocyte antigen G with chimeric antigen receptors of natural killer cells convert immunosuppression to ablate solid tumors

2021 ◽  
Vol 9 (10) ◽  
pp. e003050
Author(s):  
Chia-Ing Jan ◽  
Shi-Wei Huang ◽  
Peter Canoll ◽  
Jeffrey N Bruce ◽  
Yu-Chuan Lin ◽  
...  
Keyword(s):  
Human Leukocyte Antigen ◽  
Natural Killer ◽  
Solid Tumors ◽  
Low Dose ◽  
Human Leukocyte ◽  
Leukocyte Antigen ◽  
Low Dose Chemotherapy ◽  
Human Leukocyte Antigen G

BackgroundImmunotherapy against solid tumors has long been hampered by the development of immunosuppressive tumor microenvironment, and the lack of a specific tumor-associated antigen that could be targeted in different kinds of solid tumors. Human leukocyte antigen G (HLA-G) is an immune checkpoint protein (ICP) that is neoexpressed in most tumor cells as a way to evade immune attack and has been recently demonstrated as a useful target for chimeric antigen receptor (CAR)-T therapy of leukemia by in vitro studies. Here, we design and test for targeting HLA-G in solid tumors using a CAR strategy.MethodsWe developed a novel CAR strategy using natural killer (NK) cell as effector cells, featuring enhanced cytolytic effect via DAP12-based intracellular signal amplification. A single-chain variable fragment (scFv) against HLA-G is designed as the targeting moiety, and the construct is tested both in vitro and in vivo on four different solid tumor models. We also evaluated the synergy of this anti-HLA-G CAR-NK strategy with low-dose chemotherapy as combination therapy.ResultsHLA-G CAR-transduced NK cells present effective cytolysis of breast, brain, pancreatic, and ovarian cancer cells in vitro, as well as reduced xenograft tumor growth with extended median survival in orthotopic mouse models. In tumor coculture assays, the anti-HLA-G scFv moiety promotes Syk/Zap70 activation of NK cells, suggesting reversal of the HLA-G-mediated immunosuppression and hence restoration of native NK cytolytic functions. Tumor expression of HLA-G can be further induced using low-dose chemotherapy, which when combined with anti-HLA-G CAR-NK results in extensive tumor ablation both in vitro and in vivo. This upregulation of tumor HLA-G involves inhibition of DNMT1 and demethylation of transporter associated with antigen processing 1 promoter.ConclusionsOur novel CAR-NK strategy exploits the dual nature of HLA-G as both a tumor-associated neoantigen and an ICP to counteract tumor spread. Further ablation of tumors can be boosted when combined with administration of chemotherapeutic agents in clinical use. The readiness of this novel strategy envisions a wide applicability in treating solid tumors.

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