Department of Gynecology and Obstetrics, Development and Related Diseases of Women and Children Key Laboratory of Sichuan Province, Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, West China Second Hospital, Sichuan University, Chengdu, Sichuan, China.
Front Immunol. 2022 Nov 3;13:1035997. doi: 10.3389/fimmu.2022.1035997. eCollection 2022.
Immunotherapies have shown modest benefits in the current clinical trials for ovarian cancer. The tumor microenvironment (TME) in an immunosuppressive phenotype contributes to this "failure" of immunotherapy in ovarian cancer. Many stromal cell types in the TME (e.g., tumor-associated macrophages and fibroblasts) have been identified as having plasticity in pro- and antitumor activities and are responsible for suppressing the antitumor immune response. Thus, the TME is an extremely valuable target for adjuvant interventions to improve the effects of immunotherapy. The current strategies targeting the TME include: 1) eliminating immunosuppressive cells or transforming them into immunostimulatory phenotypes and 2) inhibiting their immunosuppressive or pro-tumor production. Most of the effective agents used in the above strategies are genetic materials (e.g., cDNA, mRNA, or miRNA), proteins, or other small molecules (e.g., peptides), which are limited in their target and instability. Various formulations of drug delivery system (DDS) have been designed to realize the controlled release and targeting delivery of these agents to the tumor sites. Nanoparticles and liposomes are the most frequently exploited materials. Based on current evidence from preclinical and clinical studies, the future of the DDS is promising in cancer immunotherapy since the combination of agents with a DDS has shown increased efficacy and decreased toxicities compared with free agents. In the future, more efforts are needed to further identify the hallmarks and biomarkers in the ovarian TME, which is crucial for the development of more effective, safe, and personalized DDSs.
免疫疗法在卵巢癌的当前临床试验中显示出适度的益处。免疫抑制表型的肿瘤微环境（TME）导致免疫疗法在卵巢癌中“失败”。TME 中的许多基质细胞类型（例如，肿瘤相关巨噬细胞和成纤维细胞）已被确定具有促肿瘤和抗肿瘤活性的可塑性，并负责抑制抗肿瘤免疫反应。因此，TME 是辅助干预以改善免疫疗法效果的极具价值的靶标。目前针对 TME 的策略包括：1）消除免疫抑制细胞或将其转化为免疫刺激表型，2）抑制其免疫抑制或促肿瘤产生。上述策略中使用的大多数有效药物都是遗传物质（例如 cDNA、mRNA 或 miRNA）、蛋白质或其他小分子（例如肽），其靶向性和稳定性有限。已经设计了各种药物递送系统（DDS）制剂，以实现这些药物在肿瘤部位的控制释放和靶向递送。纳米颗粒和脂质体是最常被利用的材料。基于临床前和临床研究的现有证据，DDS 在癌症免疫疗法中的未来前景广阔，因为与游离药物相比，DDS 与药物联合使用显示出更高的疗效和更低的毒性。未来，需要进一步努力来确定卵巢 TME 的特征和生物标志物，这对于开发更有效、安全和个性化的 DDS 至关重要。
