Paul P, Rouas-Freiss N, Khalil-Daher I, Moreau P, Riteau B, Le Gal F A, Avril M F, Dausset J, Guillet J G, Carosella E D
Direction des Sciences du Vivant-Department de Recherche Medicale, Service de Recherches en Hemato-Immunologie, Commissariat à l'Energie Atomique, Hôpital Saint-Louis, Centre Hayem, 1, Avenue Claude-Vellefaux, 75010 Paris, France.
Proc Natl Acad Sci U S A. 1998 Apr 14;95(8):4510-5. doi: 10.1073/pnas.95.8.4510.
Considering the well established role of nonclassical HLA-G class I molecules in inhibiting natural killer (NK) cell function, the consequence of abnormal HLA-G expression in malignant cells should be the escape of tumors from immunosurveillance. To examine this hypothesis, we analyzed HLA-G expression and NK sensitivity in human malignant melanoma cells. Our analysis of three melanoma cell lines and ex vivo biopsy demonstrated that (i) IGR and M74 human melanoma cell lines exhibit a high level of HLA-G transcription with differential HLA-G isoform transcription and protein expression patterns, (ii) a higher level of HLA-G transcription ex vivo is detected in a skin melanoma metastasis biopsy compared with a healthy skin fragment from the same individual, and (iii) HLA-G protein isoforms other than membrane-bound HLA-G1 protect IGR from NK lysis. It thus appears of critical importance to consider the specific role of HLA-G expression in tumors in the design of future cancer immunotherapies.
鉴于非经典HLA-G I类分子在抑制自然杀伤（NK）细胞功能方面已确立的作用，恶性细胞中HLA-G表达异常的后果应该是肿瘤逃避免疫监视。为了检验这一假设，我们分析了人类恶性黑色素瘤细胞中的HLA-G表达和NK敏感性。我们对三种黑色素瘤细胞系和离体活检的分析表明：（i）IGR和M74人类黑色素瘤细胞系表现出高水平的HLA-G转录，具有不同的HLA-G异构体转录和蛋白质表达模式；（ii）与来自同一个体的健康皮肤片段相比，在皮肤黑色素瘤转移活检中检测到离体时更高水平的HLA-G转录；（iii）除膜结合型HLA-G1外的其他HLA-G蛋白质异构体可保护IGR免受NK细胞裂解。因此，在未来癌症免疫疗法的设计中考虑HLA-G表达在肿瘤中的特定作用显得至关重要。
