HLA-G expression in melanoma: A way for tumor cells to escape from immunosurveillance

Paul, Pascale; Rouas‐Freiss, Nathalie; Khalil-Daher, Iman; Moreau, Philippe; Riteau, Béatrice; Gál, Ferenc; Avril, Marie Françoise; Dausset, J; Guillet, Jean‐Gérard; Carosella, Edgardo D.

doi:10.1073/pnas.95.8.4510

Cited by 389 publications

(305 citation statements)

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“…20 M8 is an HLA-A, -B, -C, -E-positive, HLA-G-negative melanoma cell line (HLA-A1, -A2, -B12 and -B40/male), as previously described. 31 The NK cell line NKL has been previously described. 33 Cells were maintained in RPMI 1640 medium (Sigma-Aldrich, Saint Quentin Fallavier, France) containing 10% FCS (Biological Industries, Beit Haemek, Israel).…”

Section: Cell Lines and Antibodiesmentioning

confidence: 99%

“…27 Although both receptors have other HLA class I ligands, their highest affinity is for HLA-G. 28 KIR2DL4/p49 (CD158d) was also described as an HLA-G-specific receptor expressed by all NK cells. 29,30 Following our previous studies that described HLA-G expression in tumor lesions, such as melanomas, 5,31,32 we analyzed here the mechanisms by which both expression and function of HLA-G are regulated in malignant cells.…”

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confidence: 99%

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Switch ofHLA-G alternative splicing in a melanoma cell line causes loss of HLA-G1 expression and sensitivity to NK lysis

et al. 2005

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these points by studying a melanoma cell line derived from a surgically-removed HLA-G-positive melanoma lesion. We show that HLA-G expression in melanoma cells can be regulated at the mRNA splicing level. Indeed, melanoma cells rapidly switched from cell-surface HLA-G1 to intra-cellular HLA-G2 expression. This mechanism restored tumor sensitivity to NK lysis. Moreover, switch from HLA-G1 to HLA-G2 was strong enough to prevent re-expression of immunoprotective HLA-G1 even following treatments with cytokines and DNA demethylating agent. Modulating HLA-G at the mRNA splicing level would be an efficient way of lifting in vivo HLA-G-mediated tumor immune escape. ' 2005 Wiley-Liss, Inc.

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Section: Cell Lines and Antibodiesmentioning

confidence: 99%

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confidence: 99%

Switch ofHLA-G alternative splicing in a melanoma cell line causes loss of HLA-G1 expression and sensitivity to NK lysis

et al. 2005

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“…19,20 Further, HLA-G expression has been reported in a number of malignancies 21 where it may function as a means of tumor escape from immune surveillance. [21][22][23] Membrane-bound and soluble HLA-G exerts immunosuppressive effects via interaction with inhibitory receptors ILT2, ILT4 and KIR2DL4, differentially expressed by NK, T cells and antigen-presenting cells. 18,21 Alternatively, HLA-G may serve as a leader sequence allowing for the expression of HLA-E, a cell surface inhibitory protein for which most NK cells express the receptor (CD94/NKG2A/B).…”

Section: Introductionmentioning

confidence: 99%

NK resistance of tumor cells from multiple myeloma and chronic lymphocytic leukemia patients: implication of HLA-G

et al. 2008

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Exploiting the antitumor effect of natural killer (NK) cells has regained interest in light of data from preclinical and clinical work on the potential of alloreactive NK cells. Multiple myeloma (MM) and chronic lymphocytic leukemia (CLL) represent the two most prevalent adult hematological malignancies in the western hemisphere. To evaluate the role of NK cells in the immune surveillance and their therapeutic potential for CLL and MM, tumor cell susceptibility to NK-mediated killing was investigated. Results show relative resistance of tumor cells from CLL as well as MM (73 and 70% of the patients, respectively) to NK-mediated killing. To gain insight into molecular mechanisms of this resistance, the expression of the tolerogenic HLA-G molecule in CLL and MM and its relevance to susceptibility to NK-mediated killing were investigated. HLA-G transcript was found in tumor cells from 89% (n ¼ 19) of CLL and 100% (n ¼ 9) of MM patients examined. HLA-G1 surface expression was observed in CLL and was very low or undetectable in MM. Notably, blocking of HLA-G1 with specific antibody on CLL samples increased their susceptibility to NK-mediated killing, demonstrating that HLA-G participates in protecting CLL cells from NK-mediated killing and may thus contribute to their immune escape in vivo.

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“…The absence of class II genes transcription signals down-regulate antigens processing/presenting machinery and Th1 cells communication with other cells of the immune system (Chaux et al, 1996;Paul et al, 1998). In non-mammals, the antigen processing machinery is under the control of class I genes transcription, because class I/lmp/TAP genes are closely connected on the same chromosomal loci (Kasahara et al, 1996(Kasahara et al, , 1997Kaufman and Wallny, 1996).…”

Section: Tumors In Mammals and Other Classes Of Vertebratesmentioning

confidence: 99%

“…Also, trophoblast and tumor cells can express unusual forms and numbers of MHC molecules like HLA-G and HLA-C. These molecules may mediate inhibition of antigen-specific lysis by cytotoxic T lymphocytes (CTL) and antigen-nonspecific lysis by NK cells (Paul et al, 1998). For these reasons, Lentz's belief that acquired tolerance to MHC incompatible tissue provides mechanisms for the immunotolerance of cancers cells is not valid on the whole.…”

Section: Introductionmentioning

confidence: 99%

Ideas in Theoretical Biology - Failure of Anti-Tumor Immunity in Mammals - Evolution of the Hypothesis

Bubanovic

Najman²

2004

Acta Biotheor

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Observations on the morphological and functional similarity between embryonic or trophoblast tissues and tumors are very old. Over a period of time many investigators have created different hypotheses on the origin of cancerogenesis or tumor efficiency in relation to the host immune system. Some of these ideas have been rejected but many of them are still current. A presumption of the inefficiency of anti-tumor immunity in mammals due to the high similarity between trophoblast and embryonic cells to tumor cells is very real. The mechanisms for the escape of tumors from the immune response are very similar to the mechanisms for the escape of a fetoplacental unit from the maternal immune response. The similarity between these two mechanisms is so great that any randomness must be banished. At the same time, an incidence of malignant tumors and the types of more frequent tumors in non-mammalian vertebrates is significantly different to that in mammals. Lastly, the mechanisms of anti-tumor immunity in mammals are substantially different from the mechanisms of anti-tumor immunity in other classes of vertebrates. These facts indicate that the immune system of mammals during anti-tumor immune response is tricked by the similarity between tumor cells and trophoblast or other placental cells. From this aspect, our conclusion is that anti-tumor immunity failure in mammals can be defined as an immunoreproductive phenomenon, which is developed under the evolutionary pressure of autoimmunity and reproductive effectiveness.

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HLA-G expression in melanoma: A way for tumor cells to escape from immunosurveillance

Abstract: ABSTRACT

Cited by 389 publications

References 41 publications

Switch ofHLA-G alternative splicing in a melanoma cell line causes loss of HLA-G1 expression and sensitivity to NK lysis

Switch ofHLA-G alternative splicing in a melanoma cell line causes loss of HLA-G1 expression and sensitivity to NK lysis

NK resistance of tumor cells from multiple myeloma and chronic lymphocytic leukemia patients: implication of HLA-G

Ideas in Theoretical Biology - Failure of Anti-Tumor Immunity in Mammals - Evolution of the Hypothesis

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