Wieder Thomas, Brenner Ellen, Braumüller Heidi, Röcken Martin
Department of Dermatology, Eberhard Karls University, Tübingen, Germany.
J Dtsch Dermatol Ges. 2016 Jan;14(1):28-37. doi: 10.1111/ddg.12819.
Forty years of research have brought about the development of antibodies that induce effective antitumor immune responses through sustained activation of the immune system. These "immune checkpoint inhibitors" are directed against immune inhibitory molecules, such as cytotoxic T lymphocyte antigen 4 (CTLA-4), programmed death 1 (PD-1) or programmed death ligand 1 (PD-L1). Disruption of the PD-1/PD-L1 interaction improves the intermediate-term prognosis even in patients with advanced stage IV melanoma. One and a half years after treatment initiation, 30-60 % of these patients are still alive. While cancer immunotherapies usually do not eradicate metastases completely, they do cause a regression by 20-80 %. It is well established that the immune system is able to kill tumor cells, and this has also been demonstrated for immunotherapies. Preclinical data, however, has shown that anti-cancer immunity is not limited to killing cancer cells. Thus, through interferon gamma and tumor necrosis factor, the immune system is able to induce stable tumor growth arrest, referred to as senescence. Ensuring patient survival by long-term stabilization of metastatic growth will therefore become a central goal of antitumor immunotherapies. This therapeutic approach is effective in melanoma and non-small-cell lung cancer. Once immunotherapies also have an indication for common cancer types, drug prices will have to drop considerably in order to be able to keep them available to those dependent on such therapies.
四十年的研究带来了能够通过持续激活免疫系统诱导有效抗肿瘤免疫反应的抗体的发展。这些“免疫检查点抑制剂”针对免疫抑制分子，如细胞毒性T淋巴细胞抗原4（CTLA-4）、程序性死亡受体1（PD-1）或程序性死亡配体1（PD-L1）。即使在晚期IV期黑色素瘤患者中，破坏PD-1/PD-L1相互作用也能改善中期预后。治疗开始一年半后，这些患者中有30%-60%仍然存活。虽然癌症免疫疗法通常不能完全根除转移灶，但它们确实能使肿瘤缩小20%-80%。免疫系统能够杀死肿瘤细胞，这一点已经得到证实，免疫疗法也证明了这一点。然而，临床前数据表明，抗癌免疫不限于杀死癌细胞。因此，通过γ干扰素和肿瘤坏死因子，免疫系统能够诱导稳定的肿瘤生长停滞，即衰老。因此，通过长期稳定转移灶生长来确保患者生存将成为抗肿瘤免疫疗法的核心目标。这种治疗方法在黑色素瘤和非小细胞肺癌中有效。一旦免疫疗法也适用于常见癌症类型，为了让依赖此类疗法的患者能够使用，药物价格将不得不大幅下降。
