Department of Obstetrics and Gynecology, Medical University Innsbruck, Innsbruck, Austria
Department of Obstetrics and Gynecology, Medical University Innsbruck, Innsbruck, Austria.
Int J Gynecol Cancer. 2019 Jan;29(1):201-211. doi: 10.1136/ijgc-2018-000011.
Cancer immunotherapy has emerged as one of the most promising approaches in oncology, and comprises the activation of the immune system to induce tumor immune surveillance or to reverse the tumor immune escape. Different therapeutic strategies for ovarian carcinoma have evolved over the years. Already 30 years ago, the first clinical studies focused on modulating the tumor cytokine network with special attention to interferon-mediated immune responses. With the exploration of specific tumor antigens such as NY-ESO-1, which is expressed in ovarian carcinoma and other malignancies, the development of therapeutic cancer vaccines has been pursued initiating the era of personalized anti-cancer medicine. Almost at the same time, the adoptive transfer of genetically modified autologous tumor-reactive T-cells occurred, but response rates in ovarian carcinoma were disappointing. Today, probably the most promising therapeutic approach in this context is the blockade of immune checkpoints, such as programed cell death protein 1 (PD-1) and one of its ligands (PD-L1) or cytotoxic T-cell lymphocyte-associated antigen 4 (CTLA-4), which has demonstrated impressive response rates in malignant melanoma and non-small cell lung cancer. Despite increasing availability of treatment approaches that target tumor immune surveillance in ovarian carcinoma, selecting patient groups that particularly benefit from these treatment modalities is clinically challenging as predictive biomarkers are lacking. Here, we summarize different immunotherapy approaches in ovarian cancer and discuss why immunotherapy in ovarian cancer is still in its infancy.
癌症免疫疗法已成为肿瘤学中最有前途的方法之一，包括激活免疫系统以诱导肿瘤免疫监测或逆转肿瘤免疫逃逸。多年来，针对卵巢癌的不同治疗策略不断发展。早在 30 年前，第一批临床研究就专注于调节肿瘤细胞因子网络，特别关注干扰素介导的免疫反应。随着对 NY-ESO-1 等特定肿瘤抗原的探索，该抗原在卵巢癌和其他恶性肿瘤中表达，治疗性癌症疫苗的开发已经启动，开创了个性化抗癌药物的时代。几乎在同一时间，发生了基因修饰的自体肿瘤反应性 T 细胞的过继转移，但卵巢癌的反应率令人失望。今天，在这方面最有前途的治疗方法可能是阻断免疫检查点，如程序性细胞死亡蛋白 1 (PD-1)及其配体之一（PD-L1）或细胞毒性 T 淋巴细胞相关抗原 4 (CTLA-4)，在恶性黑色素瘤和非小细胞肺癌中已显示出令人印象深刻的反应率。尽管针对卵巢癌肿瘤免疫监测的治疗方法越来越多，但由于缺乏预测性生物标志物，选择特别受益于这些治疗方式的患者群体在临床上具有挑战性。在这里，我们总结了卵巢癌中的不同免疫治疗方法，并讨论了为什么卵巢癌的免疫治疗仍处于起步阶段。
