HLA-G in Health and Disease: Comprehensive Insights and Future Therapeutic Directions

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About this Research Topic

Submission deadlines

  1. Manuscript Summary Submission Deadline 4 April 2025 | Manuscript Submission Deadline 22 July 2025

  2. This Research Topic is still accepting articles.

Background

Human Leukocyte Antigen-G (HLA-G) is a non-classical Major Histocompatibility Complex (MHC) class I molecule involved in immunotolerance induction. It modulates immune responses by engaging with inhibitory receptors (ILT2, ILT4, KIR2DL4, and CD160) found in T cells, NK cells, B cells, and dendritic cells. Under physiological conditions, HLA-G expression is tightly regulated at both transcriptional and post-transcriptional levels and limited to immune-privileged tissues to restrict local immune responses and reduce inflammation. During pregnancy, HLA-G expression at the materno-fetal interface by extravillous cytotrophoblast cells induces immune tolerance to tolerate the fetus. Interestingly, placenta and cancer genesis have common characteristics, and neoexpression of HLA-G is commonly observed in solid and hematopoietic malignancies. In this context, HLA-G protects the tumor cells from immune cells and participates in an immunosuppressive microenvironment, leading to immune evasion mechanisms. As a result, HLA-G represents a promising immune checkpoint to target, and HLA-G based therapeutic strategies are now developing.

Immune tolerance is a vital mechanism in human immunology, balancing the prevention of harmful immune responses with the need to respond effectively to pathogens. HLA-G, as potent immunotolerance inducer, plays a central role in maintaining this delicate equilibrium and interferes in diverse contexts. Indeed, studies on HLA-G and its receptors cover a broad range of topics, including reproductive biology (pregnancy and endometrial diseases), allergy, auto-immune diseases, viral infections, transplantation, and oncology.
Given its potential as a biomarker and therapeutic target, the research on HLA-G has drastically accelerated in the last decade and induced a growing interest in the general scientific community. Both induction or blocking of HLA-G/receptors interactions show promising results, even though the underlying mechanisms are not fully understood.
This special issue aims to bring together current knowledge and recent discoveries of the various aspects of HLA-G biology. By identifying parallels across different research fields, this issue intends to foster interdisciplinary connections, ultimately driving forward the development of HLA-G-targeted therapies. Our goal is to create a comprehensive resource that provides both fundamental knowledge and promotes insights into the clinical applications of HLA-G research.

This special issue invites a diverse range of contributions related to HLA-G and its receptors, encompassing the full spectrum of HLA-G biology. We welcome contributions in various formats, from original research articles, reviews, methodological papers, short communications, and evaluation of clinical trials. To gather further insights into the mechanisms and impacts of HLA-G, we welcome articles addressing, but not limited to, the following themes:

o HLA-G expression in pregnancy and reproductive biology
o The role of HLA-G in cancer immune evasion and tumor-host interactions
o Implications of HLA-G in autoimmune diseases and transplantation
o Innovations in HLA-G-targeted therapeutic strategies
o Evaluations of clinical trials focusing on HLA-G interventions
o Cross-disciplinary research connecting HLA-G functions across various diseases

By synthesizing current knowledge and promoting novel research, this special issue aims to enhance our understanding of HLA-G's biology and foster the development of targeted therapies. It encourages submissions that push the boundaries of traditional research frameworks, offering a platform for breakthrough findings that could translate into clinical innovations.

Article types and fees

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

  • Brief Research Report
  • Case Report
  • Classification
  • Clinical Trial
  • Editorial
  • General Commentary
  • Hypothesis and Theory
  • Methods
  • Mini Review

Articles that are accepted for publication by our external editors following rigorous peer review incur a publishing fee charged to Authors, institutions, or funders.

Keywords: HLA-G, ILT2, ILT4, LILRB1, LILRB2, KIR2DL4, CD160, Immune tolerance, Immunotherapy, Pregnancy and endometrial disease, Transplantation

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