CEA, IMETI, Service de Recherches en Hemato-Immunologie, Paris, France.
Eur J Immunol. 2012 Jun;42(6):1599-608. doi: 10.1002/eji.201141761.
Dimers of the nonclassical HLA-G class I molecule have recently been shown to be active structures that mediate inhibition of NK-cell cytotoxic activity through interaction with the immunoglobulin-like transcript (ILT)-2 inhibitory receptor. However, this has only been proven in trophoblasts and HLA-G transfectants. Here, we document for the first time the existence of HLA-G dimers in cancer. Indeed, we identified both surface and soluble HLA-G dimers in tumor cells and malignant ascites respectively. Interestingly, factors from the tumor microenvironment, such as interferons, enhanced the formation of HLA-G dimers and increased the protection of tumors from NK cell-mediated lysis. These data emphasize the impact of HLA-G conformation on its efficiency at inhibiting the antitumor response and thus favoring tumor progression. In view of these results, the effect of the tumor microenvironment on upregulation of HLA-G function deserves particular attention when designing cancer immunotherapy protocols.
最近的研究表明，非经典 HLA-G 类 I 分子的二聚体是具有活性的结构，通过与免疫球蛋白样转录物（ILT）-2 抑制性受体相互作用，介导 NK 细胞细胞毒性活性的抑制。然而，这仅在滋养层细胞和 HLA-G 转染细胞中得到证实。在这里，我们首次在癌症中证明了 HLA-G 二聚体的存在。事实上，我们分别在肿瘤细胞和恶性腹水中鉴定到了表面和可溶性 HLA-G 二聚体。有趣的是，肿瘤微环境中的因子，如干扰素，增强了 HLA-G 二聚体的形成，并增加了肿瘤对 NK 细胞介导的裂解的保护。这些数据强调了 HLA-G 构象对其抑制抗肿瘤反应效率的影响，从而有利于肿瘤的进展。鉴于这些结果，在设计癌症免疫治疗方案时，肿瘤微环境对 HLA-G 功能上调的影响值得特别关注。
