Sun Xuan, Li Min, Wang Peng, Bai Qingqing, Cao Xuchen, Mao Duo
The First Department of Breast Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, and Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University, Ministry of Education, Tianjin, 300060, China.
Precision Medicine Institute, The First Affiliated Hospital of Sun Yat-sen University, Sun Yat-sen University, Guangzhou, 510080, China.
Small Methods. 2023 May;7(5):e2201614. doi: 10.1002/smtd.202201614. Epub 2023 Mar 24.
In the past decades, immunotherapy has achieved a series of clinical successes in the field of cancer. However, existing therapeutic options usually show a low immune response to solid tumors caused by immunosuppressive "cold" tumor microenvironment (TME). Several types of proinflammatory regulated cell death (RCD), mainly including ferroptosis and pyroptosis, have been studied recently, which can provide proinflammatory signals and immunogenicity necessary for remodeling TME and activating an antitumor immune response. A variety of chemotherapeutic drugs are proven to be effective in the proinflammatory RCD induction of tumor cells, but several adverse effects and intrinsic drug resistance usually occur in the therapeutic process, greatly hindering their further clinical application. The emerging organic photosensitizer (PS)-based materials open new possibilities to effectively activate proinflammatory RCD through precise spatiotemporal regulation of intracellular reactive oxygen species-associated signaling pathways, which can overcome many challenges encountered in current proinflammatory RCD-mediated immunotherapy. In this review, the recent design strategies of PS probes are detailly summarized and their potential advantages for tumor-specific proinflammatory RCD induction are discussed. Moreover, the representative examples in cancer immunotherapy are highlighted and future perspectives in this emerging field are proposed.
在过去几十年中，免疫疗法在癌症领域取得了一系列临床成功。然而，由于免疫抑制性“冷”肿瘤微环境（TME），现有的治疗方案通常对实体瘤表现出低免疫反应。最近研究了几种促炎性调节性细胞死亡（RCD），主要包括铁死亡和焦亡，它们可以提供重塑TME和激活抗肿瘤免疫反应所需的促炎信号和免疫原性。多种化疗药物被证明在诱导肿瘤细胞发生促炎性RCD方面有效，但在治疗过程中通常会出现一些不良反应和内在耐药性，极大地阻碍了它们的进一步临床应用。新兴的基于有机光敏剂（PS）的材料通过对细胞内活性氧相关信号通路进行精确的时空调控，为有效激活促炎性RCD开辟了新的可能性，这可以克服当前促炎性RCD介导的免疫疗法中遇到的许多挑战。在这篇综述中，详细总结了PS探针的最新设计策略，并讨论了它们在肿瘤特异性促炎性RCD诱导方面的潜在优势。此外，突出了癌症免疫疗法中的代表性实例，并提出了这一新兴领域的未来展望。
