Given the success of Volume I of this Research Topic, and the rapidly evolving subject area, we are pleased to announce the launch of Volume II: The Biological and Clinical Aspects of HLA-G.

Human leukocyte antigen G (HLA-G) is an important immune regulator in homeostasis and disease progression. With alternative splicing of its primary transcript, seven isoforms including four-membrane bound (HLA-G1, -G2, -G3, and -G4) and three soluble (HLA-G5, -G6, and -G7) molecules have been acknowledged, and more novel isoforms remain to be validated. Multiple receptors such as (immunoglobulin-like transcripts 2/ILT2, ILT4, KIR2DL4, etc.) have been recognized to interact with HLA-G. Consequently, HLA-G can exert various biological functions through receptor interaction and signaling. Cell surface expressed and intercellular transferred HLA-G and receptor signaling pathway have been observed to be involved in various physiological and pathological conditions, such as benefit fetal-maternal immune tolerance and prolong transplanted grafts acceptance, while impair host immune responses against virally infected cells and malignant cells and enhance the capability of these abnormal cells to escape immune clearance.

Much progress has been achieved during the past three decades, such as early clinical trials with HLA-G antibodies for solid cancer immunotherapy are launched, and functional pre-clinical therapeutic CAR-T cells against HLA-G were established. However, many aspects of HLA-G remain to be explored, especially in the molecular mechanisms of immune regulation by different HLA-G isoforms, the clinical significance of heterogeneous HLA-G expression as well as pre-clinical and clinical evidence of HLA-G functions as an immune checkpoint in cancer therapies, and in other physio-pathological settings.

The goal of this Research Topic is to focus on the latest advances in biological and clinical significance of HLA-G. We welcome submissions of Review, Mini-Review, Opinion, as well as Original Research articles focusing on, but not strictly limited to the following topics:

1. Molecular mechanisms of HLA-G function and receptor interaction, particularly different HLA-G isoforms, and polymers

2. Functional roles of HLA-G by intercellular transfer, such as exosome and trogocytosis

3. Clinical significance of both genetic aspects and HLA-G expression in cancer, transplantation, reproduction, autoimmune and infectious diseases, etc.

4. Novel reagents and methods for HLA-G analysis, such as HLA-G-isoform specific antibody development and new detection protocols

5. Development and therapeutic potential of HLA-G-based immunotherapy in various pathological settings

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Frontiers in Immunology

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