Bazhin Alexandr V, Schadendorf Dirk, Philippov Pavel P, Eichmüller Stefan B
Skin Cancer Unit (D070), German Cancer Research Center, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
Cancer Immunol Immunother. 2007 Jan;56(1):110-6. doi: 10.1007/s00262-006-0132-z.
In photoreceptor cells the Ca(2+) -binding protein recoverin controls phosphorylation of the visual receptor rhodopsin by inhibiting rhodopsin kinase (GRK-1). It can also serve as a paraneoplastic antigen in the development of retinal degeneration in some patients with cancer. The aberrant expression of recoverin in cancer cells and the presence of autoantibodies against recoverin are essential for the occurrence of cancer-associated retinopathy, which finally results in the apoptosis of photoreceptor cells. Noteworthy in cancer patients, the aberrant recoverin expression and the appearance of autoantibodies against recoverin are more frequent than paraneoplastic syndromes. We suggest the term "cancer-retina antigens" for this kind of proteins like recoverin that are solely expressed in retina and tumor tissues and evoke antibodies and/or T cells in patients with cancer. The rare development of a paraneoplastic syndrome is possibly caused by this immune response and probably depends on further events allowing to overcome the blood-retina barrier and the immune privileged status of the retina. It is still unknown whether aberrantly expressed recoverin could have a specific function in cancer cells, though it is suggested that it can be functionally associated with G-protein-coupled receptor kinases. This paper reviews the present knowledge on paraneoplastic syndromes associated with the aberrant expression of recoverin. A possible application of recoverin as a potential target for immunotherapy of cancer is discussed.
在光感受器细胞中,钙结合蛋白恢复蛋白通过抑制视紫红质激酶(GRK-1)来控制视觉受体视紫红质的磷酸化。在一些癌症患者视网膜变性的发生过程中,恢复蛋白还可作为一种副肿瘤抗原。癌细胞中恢复蛋白的异常表达以及针对恢复蛋白自身抗体的存在,对于癌症相关性视网膜病变的发生至关重要,最终导致光感受器细胞凋亡。值得注意的是,在癌症患者中,恢复蛋白的异常表达以及针对恢复蛋白自身抗体的出现比副肿瘤综合征更为常见。对于像恢复蛋白这类仅在视网膜和肿瘤组织中表达,并在癌症患者体内引发抗体和/或T细胞的蛋白质,我们建议使用“癌-视网膜抗原”这一术语。副肿瘤综合征的罕见发生可能是由这种免疫反应引起的,并且可能取决于进一步能够突破血视网膜屏障和视网膜免疫赦免状态的事件。尽管有研究表明恢复蛋白可能与G蛋白偶联受体激酶存在功能关联,但目前仍不清楚异常表达的恢复蛋白在癌细胞中是否具有特定功能。本文综述了与恢复蛋白异常表达相关的副肿瘤综合征的现有知识,并讨论了恢复蛋白作为癌症免疫治疗潜在靶点的可能应用。