Intercellular transfer of HLA‐G: its potential in cancer immunology

Lin, Aifen; Yan, Wei‐Hua

doi:10.1002/cti2.1077

Cited by 36 publications

(31 citation statements)

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“…The HLA-G gene consists of eight exons, seven introns, a 5 ′ upstream regulatory region (URR) that extends at least 1,400 bp from the initial ATG start codon, and a 3 ′ untranslated region (UTR), with a total length of 6,000 bp (12,17). It is widely accepted that the HLA-G primary transcript is alternatively spliced into seven mRNAs, which encode four membrane-bound (HLA-G1, -G2, -G3, -G4) and three soluble (HLA-G5, -G6, -G7) protein isoforms (18,19).…”

Section: Molecular Structure Of Human Leukocyte Antigen-gmentioning

confidence: 99%

“…Functionally, HLA-G has comprehensive immunosuppressive properties exerted in multiple steps to weaken antitumor immune responses by acting on immune cells through its inhibitory receptors: ILT2(CD85j/LILRB1), ILT4(CD85d/LILRB2), and KIR2DL4(CD158d) (11,12,(55)(56)(57)(58)(59) (Figure 1). HLA-G inhibits the cytolytic function of natural killer (NK) cells (60,61), cytotoxic T lymphocyte (CTL)mediated cytolysis (62), macrophage-mediated cytotoxicity (63), allo-proliferative response of CD4 + T cells (64,65), maturation and function of dendritic cells (DCs) or B lymphocytes (66)(67)(68)(69), stimulation of antigen-presenting cells (APCs) to secrete functional cytokines TGF-β and IL-10, and induction of apoptosis of CD8 + T cells and CD8 + NK cells (70,71).…”

Section: Hla-g-mediated Immune Suppressionmentioning

confidence: 99%

“…HLA-G has been termed "non-classical" due to its low frequency of polymorphisms, restricted tissue distribution and immunoinhibitory properties, which are different from the properties of classical HLA-class I molecules (10,11). It has become increasingly evident that the HLA-G molecule is involved in modulating both innate and adaptive immune responses and in promoting immune escape in various types of cancers (10)(11)(12)(13) and infectious diseases (14)(15)(16). However, to date, the possibility that HLA-G gene polymorphisms and/or protein expression affecting HPV infection persistence and cervical cancer risk remains to be explored.…”

Section: Introductionmentioning

confidence: 99%

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The Role of HLA-G in Human Papillomavirus Infections and Cervical Carcinogenesis

Xu¹,

Yan²,

Lin³

2020

Front. Immunol.

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Human leukocyte antigen (HLA)-G, a non-classical HLA-class I molecule, has a low polymorphism frequency, restricted tissue distribution and immunoinhibitory property. HLA-G expression in tumor cells and cells chronically infected with virus may enable them to escape from host immune surveillance. It is well-known that the HLA-G molecule is a novel biomarker and potential therapeutic target that is relevant in various types of cancers, but its role in cervical cancer has not been fully explored. In this review, we aim to summarize and discuss the immunologic role of the HLA-G molecule in the context of HPV infections and the process of cervical cancer carcinogenesis. A better understanding of the potential impact of HLA-G on the clinical course of persistent HPV infections, cervical epithelial cell transformation, tumor growth, recurrence and metastasis is needed to identify a novel diagnostic/prognostic biomarker for cervical cancer, which is critical for cervical cancer risk screening. In addition, it is also necessary to identify HLA-G-driven immune mechanisms involved in the interactions between host and virus to explore novel immunotherapy strategies that target HLA-G/immunoglobulin-like transcript (ILT) immune checkpoints.

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Section: Molecular Structure Of Human Leukocyte Antigen-gmentioning

confidence: 99%

Section: Hla-g-mediated Immune Suppressionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The Role of HLA-G in Human Papillomavirus Infections and Cervical Carcinogenesis

Xu¹,

Yan²,

Lin³

2020

Front. Immunol.

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“…27 HLA-G, an immunosuppressive molecule, has been reported to be transferred among tumor cells and immune cells, leading to a suppressive tumor environment and a dampened anti-tumor immunity. 28 Therefore, the effect of trogocytosis on immune responses needs to be analyzed on a case-by-case basis. 21 Below, we will summarize recent results on the effect of trogocytosis on HL.…”

Section: Trogocytosismentioning

confidence: 99%

The role of trogocytosis in immune surveillance of Hodgkin lymphoma

Zeng

Schwarz

2020

OncoImmunology

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Hodgkin lymphoma (HL) is a unique type of hematopoietic cancer that has few tumor cells but a massive infiltration of immune cells. Findings on how the cancerous Hodgkin and Reed-Sternberg (HRS) cells survive and evade immune surveillance have facilitated the development of novel immunotherapies for HL. Trogocytosis is a fast process of intercellular transfer of membrane patches, which can significantly affect immune responses. In this review, we summarize the current knowledge of how trogocytosis contributes to the suppression of immune responses in HL. We focus on the ectopic expression of CD137 on HRS cells, the cause of its expression, and its implication on developing novel therapies for HL. Further, we review data demonstrating that similar mechanisms apply to CD30, PD-L1 and CTLA-4.

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“…In addition, several approaches have been developed to block the HLA‐G/ILT signalling pathway, which take into account also the different mechanism regulating HLA‐G surface expression. These approaches include HLA‐G antagonists, blocking antibodies against HLA‐G or its receptors, siRNA, inhibition of its intercellular transfer and HLA‐G as target for drug delivery (Li et al, 2017; Lin & Yan, 2019; Zhang et al, 2014). Therefore, KIRs and HLA‐G may also represent promising targets for combined therapy.…”

Section: Combined Therapies To Improve Immune Checkpoint Blockade Effmentioning

confidence: 99%

Inhibitory checkpoints in human natural killer cells: IUPHAR Review 28

Mariotti

Quatrini

Munari

et al. 2020

British J Pharmacology

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Immune checkpoint inhibitors have revolutionized cancer therapy leading to exceptional success. However, there is still the need to improve their efficacy in nonresponder patients. Natural killer (NK) cells represent the first line of defence against tumours, due to their ability to release immunomodulatory cytokines and kill target cells that have undergone malignant transformation. Harnessing NK cell response will open new possibilities to improve control of tumour growth. In this respect inhibitory checkpoints expressed on these innate lymphocytes represents a promising target for next-generation immunotherapy. In this review, we will summarize recent evidences on the expression of NK cells receptors in cancer, with a focus on the inhibitory checkpoint programmed cell death protein 1 (PD-1). We will also highlight the strength and limitations of the blockade of PD-1 inhibitory pathway and suggest new combination strategies that may help to unleash more efficiently NK cell anti-tumour response.Abbreviations: AbE, abscopal effect; AML, acute myeloid leukaemia; BM, bone marrow; CAR, chimeric antigen receptor; CTLA-4, cytotoxic T-lymphocyte-associated protein 4; DCs, dendritic cells; Gal-9, galectin-9; GvDH, graft versus host disease; HMGB-1, high-mobility group box 1; ICIs, immune checkpoint inhibitors; ITAM, immunoreceptor tyrosine-based activation motif; ITIM, immunoreceptor tyrosine-based inhibitory motif; ITSM, immunoreceptor tyrosine-based switch motif; IDO, indoleamine 2,3-dioxygenase; iPSCs, induced pluripotent stem cells; NKG2A, killer cell lection-like receptor C1; KIRs, killer immunoglobulin (Ig)-like receptors; LILRB, leukocyte Ig-like receptor subfamily B; LAG-3, lymphocyte activation gene-3; MHC-I, major histocompatibility complex class I; mAbs, monoclonal antibodies; NCRs, natural cytotoxicity receptors; NSCLC, non-small-cell lung cancer; PB, peripheral blood; PtdSer, phospatidylserine; PD-L1, programmed cell death 1 ligand 1; PD-L2, programmed cell death 1 ligand 2; PD-1, programmed cell death protein 1; RT, radiotherapy; SHP-1 and SHP-2, SH2 domain-containing phosphatase; sPD-1, soluble form of PD-1; SCCHN, squamous cell carcinomas of the head and neck; TIGIT, T-cell immunoglobulin and ITIM domain; TIM3, T-cell immunoglobulin and mucin domain-containing protein 3;TAAs, tumour-associated antigens; TILs, tumour-infiltrating lymphocytes; TMB, tumour mutational burden; UCB, umbilical cord blood. F. R. Mariotti and L. Quatrini contributed equally to this work.

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Intercellular transfer of HLA‐G: its potential in cancer immunology

Cited by 36 publications

References 81 publications

The Role of HLA-G in Human Papillomavirus Infections and Cervical Carcinogenesis

The Role of HLA-G in Human Papillomavirus Infections and Cervical Carcinogenesis

The role of trogocytosis in immune surveillance of Hodgkin lymphoma

Inhibitory checkpoints in human natural killer cells: IUPHAR Review 28

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