Authors' Affiliation: Division of Early Drug Development for Innovative Therapies, Istituto Europeo di Oncologia, Milan, Italy.
Clin Cancer Res. 2013 Oct 15;19(20):5564-71. doi: 10.1158/1078-0432.CCR-12-3697. Epub 2013 Jul 29.
Human leukocyte antigen G (HLA-G) is a nonclassical MHC class I molecule that exerts important tolerogenic functions. Its main physiologic expression occurs in the placenta, where it participates in the maternal tolerance toward the fetus. HLA-G expression was found in embryonic tissues, in adult immune privileged organs, and in cells of the hematopoietic lineage. It is expressed in various types of primary solid (melanoma, head and neck, lung, urogenital, gastrointestinal, and breast cancers) and hematologic malignancies (acute leukemia, lymphomas) and metastases. HLA-G ectopic expression is observed in cancer, suggesting that its expression is one strategy used by tumor cells to escape immune surveillance. In this review, we will focus on HLA-G expression in cancers and its association with the prognosis. We will highlight the underlying molecular mechanisms of impaired HLA-G expression, the immune tolerant function of HLA-G in tumors, and the potential diagnostic use of membrane-bound and soluble HLA-G as a biomarker to identify tumors and to monitor disease stage. As HLA-G is a potent immunoinhibitory molecule, its blockade remains an attractive therapeutic strategy against cancer. Elimination of HLA-G-expressing cancer cells would be important in the efficacy of anticancer therapies.
人类白细胞抗原 G（HLA-G）是一种非经典 MHC Ⅰ类分子，具有重要的免疫耐受功能。其主要生理表达发生在胎盘，在胎盘处它参与母体对胎儿的耐受。HLA-G 的表达还存在于胚胎组织、成人免疫特权器官和造血谱系细胞中。它在各种原发性实体瘤（黑色素瘤、头颈部、肺、泌尿生殖、胃肠道和乳腺癌）和血液系统恶性肿瘤（急性白血病、淋巴瘤）和转移中表达。在癌症中观察到 HLA-G 异位表达，表明其表达是肿瘤细胞逃避免疫监视的一种策略。在这篇综述中，我们将重点关注 HLA-G 在癌症中的表达及其与预后的关系。我们将强调 HLA-G 表达受损的潜在分子机制、HLA-G 在肿瘤中的免疫耐受功能，以及膜结合型和可溶性 HLA-G 作为生物标志物用于识别肿瘤和监测疾病阶段的潜在诊断用途。由于 HLA-G 是一种有效的免疫抑制分子，其阻断仍然是对抗癌症的一种有吸引力的治疗策略。消除表达 HLA-G 的癌细胞对于癌症治疗的疗效很重要。
