Inhibition of human Vγ9Vδ2 T-cell antitumoral activity through HLA-G: implications for immunotherapy of cancer

Lesport, Emilie; Baudhuin, Jérémy; Sousa, Sylvie; LeMaoult, Joël; Zamborlini, Alessia; Rouas‐Freiss, Nathalie; Carosella, Edgardo D.; Favier, Benoît

doi:10.1007/s00018-011-0632-7

Cited by 54 publications

(27 citation statements)

References 65 publications

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“…Accumulation of gd T-cell receptors was previously demonstrated at the site of contact with tumor cells and no recruitment of HLA-G1 or ILT2 was observed to the gd T-cell/tumor cell interface [34,35]. Moreover, no accumulation of HLA-G1 or ILT2 was found at the inhibitory synapse formed between NK and tumor cells expressing HLA-G1 [15].…”

Section: Discussionmentioning

confidence: 81%

“…Besides NK-cell functions, HLA-G1 has also been shown to impair gd T-cell cytolytic function and IFN-g production via interaction with ILT2 [34]. Accumulation of gd T-cell receptors was previously demonstrated at the site of contact with tumor cells and no recruitment of HLA-G1 or ILT2 was observed to the gd T-cell/tumor cell interface [34,35].…”

Section: Discussionmentioning

confidence: 99%

“…Melanoma cells M8 transfected with pcDNA3.1 vector (Invitrogen) alone (M8-pcDNA) or containing the HLA-G1 cDNA (M8-HLA-G1) and the primary melanoma cell lines FON À , which does not express HLA-G and FON 1 which constitutively express HLA-G1 have been reported [34]. 721.221, M8, FON and NKL cells were cultured in RPMI 1640 (Sigma) supplemented with 2 mM L-glutamine (Invitrogen), 100 IU/mL penicillin (Invitrogen), 100 mg/mL streptomycin (Invitrogen) and 10% heatinactivated fetal calf serum (FCS, Sigma).…”

Section: Cells and Culturementioning

confidence: 99%

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HLA‐G inhibition of NK‐cell cytolytic function is uncoupled from tumor cell lipid raft reorganization

Baudhuin¹,

Lesport²,

Sousa³

et al. 2012

Eur J Immunol

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HLA-G is a non-classical HLA class I molecule with tolerogenic properties and restricted tissue distribution. The expression of HLA-G can be induced by tumors thus providing an efficient way to escape the anti-tumoral immune response. Although lipid rafts regulate diverse immunological mechanisms their relationship with HLA-G remains controversial. Our results show that HLA-G-mediated inhibition of both the interaction between NK and tumor cells, and of intracellular calcium flux in NK cells conjugated to their target cells were independent of lipid raft integrity. In addition, cytotoxicity assays indicated that HLA-G continued to efficiently inhibit NK-cell cytolytic function in several different tumor cells independently of lipid raft integrity. Confocal microscopy with 3D reconstruction combined with biochemical analysis showed that HLA-G was mainly localized outside the lipid rafts of tumor cells after cross-linking with specific antibody and remained excluded from lipid rafts during interaction with the ILT2 inhibitory receptor of NK cells. This study indicates that the inhibitory function of HLA-G is uncoupled from lipid raft organization, further distinguishing HLA-G from classical HLA molecules and providing novel information in the understanding of tumor immune escape mechanism mediated through HLA-G.

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Section: Discussionmentioning

confidence: 81%

Section: Discussionmentioning

confidence: 99%

Section: Cells and Culturementioning

confidence: 99%

See 1 more Smart Citation

HLA‐G inhibition of NK‐cell cytolytic function is uncoupled from tumor cell lipid raft reorganization

Baudhuin¹,

Lesport²,

Sousa³

et al. 2012

Eur J Immunol

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View full text Add to dashboard Cite

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“…Indirect inhibitory immune effects of HLA-G could induce the generation cytotoxicity by interacting with the ILT2 inhibitory receptor (32)(33)(34)(35). We recently reported that NK cell cytolysis inhibited by HLA-G1 in an expression proportion-dependent manner, and HLA-G1 and HLA-G5 isoforms have an additive inhibitory effect on NK cytolysis (36,37 …”

Section: Introductionmentioning

confidence: 99%

Human Leukocyte Antigen-G (HLA-G) Expression in Cancers: Roles in Immune Evasion, Metastasis and Target for Therapy

Lin

Yan

2015

Mol Med

110

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Aberrant induction of human leukocyte antigen-G (HLA-G) expression has been observed in various malignancies and is strongly associated with tumor immune escape, metastasis and poor prognosis. To date, great achievements have been made in understanding the underlying mechanisms of HLA-G involved in tumor progression. HLA-G could lead to tumor evasion by inhibition of immune cell cytolysis, differentiation and proliferation and inhibition of cytokine production, induction of immune cell apoptosis, generation of regulatory cells and expansion of myeloid-derived suppressive cells and by impairment of chemotaxis. Moreover, HLA-G could arm tumor cells with a higher invasive and metastatic potential with the upregulation of tumor-promoting factor expression such as matrix metalloproteinases (MMPs), indicating that ectopic HLA-G expression could render multiple effects during the progression of malignancies. In this review, we summarized the mechanisms of HLA-G involved in promoting tumor cell immune escaping, metastasis and disease progression. Special attention will be paid to its significance as an attractive therapeutic target in cancers.

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“…In contrast, regulatory receptors for self-MHC class I molecules, particularly KIR (Killer cell Immunoglobulin-like Receptor) and LIR (Leukocyte Immunoglobulin-like Receptor) receptors, were reported to negatively regulate γδ T-cell activation (34, 35). This inhibition is due to the presence of intracytoplasmic ITIM (Immunoreceptor Tyrosine-based Inhibitory Motif) motif in the sequence of these receptors which turn off the activation signals upon phosphorylation.…”

Section: Pleiotropic Role Of Human γδ T Cell Subsetsmentioning

confidence: 99%

Key Features of Gamma-Delta T-Cell Subsets in Human Diseases and Their Immunotherapeutic Implications

2017

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The unique features of gamma-delta (γδ) T cells, related to their antigen recognition capacity, their tissue tropism, and their cytotoxic function, make these cells ideal candidates that could be targeted to induce durable immunity in the context of different pathologies. In this review, we focus on the main characteristics of human γδ T-cell subsets in diseases and the key mechanisms that could be explored to target these cells.

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Inhibition of human Vγ9Vδ2 T-cell antitumoral activity through HLA-G: implications for immunotherapy of cancer

Cited by 54 publications

References 65 publications

HLA‐G inhibition of NK‐cell cytolytic function is uncoupled from tumor cell lipid raft reorganization

HLA‐G inhibition of NK‐cell cytolytic function is uncoupled from tumor cell lipid raft reorganization

Human Leukocyte Antigen-G (HLA-G) Expression in Cancers: Roles in Immune Evasion, Metastasis and Target for Therapy

Key Features of Gamma-Delta T-Cell Subsets in Human Diseases and Their Immunotherapeutic Implications

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