State Key Laboratory of Drug Research & Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
University of Chinese Academy of Sciences, Beijing 100049, China.
Cancer Biol Med. 2023 May 2;20(4):248-67. doi: 10.20892/j.issn.2095-3941.2023.0009.
Cancer immunotherapy, a therapeutic approach that inhibits tumors by activating or strengthening anti-tumor immunity, is currently an important clinical strategy for cancer treatment; however, tumors can develop drug resistance to immune surveillance, resulting in poor response rates and low therapeutic efficacy. In addition, changes in genes and signaling pathways in tumor cells prevent susceptibility to immunotherapeutic agents. Furthermore, tumors create an immunosuppressive microenvironment immunosuppressive cells and secrete molecules that hinder immune cell and immune modulator infiltration or induce immune cell malfunction. To address these challenges, smart drug delivery systems (SDDSs) have been developed to overcome tumor cell resistance to immunomodulators, restore or boost immune cell activity, and magnify immune responses. To combat resistance to small molecules and monoclonal antibodies, SDDSs are used to co-deliver numerous therapeutic agents to tumor cells or immunosuppressive cells, thus increasing the drug concentration at the target site and improving efficacy. Herein, we discuss how SDDSs overcome drug resistance during cancer immunotherapy, with a focus on recent SDDS advances in thwarting drug resistance in immunotherapy by combining immunogenic cell death with immunotherapy and reversing the tumor immunosuppressive microenvironment. SDDSs that modulate the interferon signaling pathway and improve the efficacy of cell therapies are also presented. Finally, we discuss potential future SDDS perspectives in overcoming drug resistance in cancer immunotherapy. We believe that this review will contribute to the rational design of SDDSs and development of novel techniques to overcome immunotherapy resistance.
癌症免疫疗法是一种通过激活或增强抗肿瘤免疫来抑制肿瘤的治疗方法，是目前癌症治疗的重要临床策略；然而，肿瘤可以对免疫监视产生耐药性，导致反应率低和治疗效果差。此外，肿瘤细胞中基因和信号通路的改变使它们对免疫治疗药物产生抗性。此外，肿瘤会产生免疫抑制微环境，免疫抑制细胞会分泌分子，阻止免疫细胞和免疫调节剂的浸润或诱导免疫细胞功能障碍。为了解决这些挑战，已经开发出智能药物递送系统（SDDS）来克服免疫调节剂对肿瘤细胞的耐药性，恢复或增强免疫细胞的活性，并放大免疫反应。为了对抗小分子和单克隆抗体的耐药性，SDDS 被用于共同递送至肿瘤细胞或免疫抑制细胞的多种治疗剂，从而增加靶部位的药物浓度并提高疗效。在此，我们讨论了 SDDS 如何在癌症免疫治疗中克服耐药性，重点介绍了最近通过将免疫原性细胞死亡与免疫治疗相结合并逆转肿瘤免疫抑制微环境来克服免疫治疗耐药性的 SDDS 进展。还介绍了调节干扰素信号通路和提高细胞治疗疗效的 SDDS。最后，我们讨论了克服癌症免疫治疗中耐药性的潜在未来 SDDS 前景。我们相信，这篇综述将有助于合理设计 SDDS 和开发克服免疫治疗耐药性的新技术。
