Department of Obstetrics and Gynecology (791), Radboud University Nijmegen Medical Centre, PO Box 9101, 6500 HB Nijmegen, The Netherlands.
Gynecol Oncol. 2010 May;117(2):366-72. doi: 10.1016/j.ygyno.2010.01.019. Epub 2010 Feb 9.
Considering the high mortality rate of ovarian cancer due to the absence of curative treatment in advanced stage or at recurrence, new therapeutic strategies are urgently needed. Immunotherapy is one of these strategies that yielded promising results in fundamental and animal research in the past years. However, implementation in clinical practice remains poor. The aim of this review is to gain insight into the mechanisms of interaction between ovarian cancer and the immune system in order to develop better immunotherapeutic strategies.
We searched the published literature for studies focusing on interactions between ovarian cancer and the immune system, with emphasis on outcome data in order to create a knowledge base that is well grounded in clinical reality.
The immunological response against cancer is a critical balance between immune-activating and immune-suppressing mechanisms. Besides the immune-activating tumor infiltrating lymphocytes (TILs), immune-suppressive regulatory T-cells (Tregs), tolerance-inducing plasmacytoid dendritic cells (pDCs), B7-H4+ macrophages, immune-suppressive cytokines such as IL10 and TGF-beta are also found in the tumor environment. Myeloid-derived suppressive cells (MDSCs) are recently found to have a significant role in immune suppression in ovarian cancer in murine studies. Furthermore, vascular endothelial growth factor (VEGF) is also known to have an immune-suppressing role besides its angiogenic role. All those concerted mechanisms result in the creation of an environment where the cancer is invincible and can grow unhampered.
Further knowledge of the mechanisms involved is needed to develop better strategies and improve the clinical applicability of immunotherapy. Effective immunotherapy must combine immune-activating strategies with elimination of immune-suppressing mechanisms. We believe that tilting the balance from an immune-suppressive to an immune-active environment may have an enormous impact on the disease.
由于在晚期或复发时缺乏治愈性治疗，卵巢癌的死亡率很高，因此迫切需要新的治疗策略。免疫疗法是这些策略之一，在过去几年的基础和动物研究中取得了有希望的结果。然而，在临床实践中的实施仍然很差。本综述的目的是深入了解卵巢癌与免疫系统之间相互作用的机制，以便开发更好的免疫治疗策略。
我们搜索了已发表的文献，重点研究了卵巢癌与免疫系统之间的相互作用，强调了结果数据，以便在临床现实中建立一个良好的知识库。
针对癌症的免疫反应是免疫激活和免疫抑制机制之间的关键平衡。除了免疫激活的肿瘤浸润淋巴细胞 (TILs) 外，还存在免疫抑制性调节性 T 细胞 (Tregs)、诱导耐受的浆细胞样树突状细胞 (pDCs)、B7-H4+巨噬细胞、免疫抑制性细胞因子如 IL10 和 TGF-beta。髓源性抑制细胞 (MDSCs) 最近在鼠类研究中被发现对卵巢癌的免疫抑制具有重要作用。此外，血管内皮生长因子 (VEGF) 除了其血管生成作用外，还具有免疫抑制作用。所有这些协同作用的机制导致了癌症不可战胜且可以不受阻碍地生长的环境的形成。
需要进一步了解所涉及的机制，以开发更好的策略并提高免疫疗法的临床适用性。有效的免疫疗法必须将免疫激活策略与消除免疫抑制机制相结合。我们相信，将平衡从免疫抑制环境倾斜到免疫激活环境可能会对疾病产生巨大影响。
