Moores Cancer Center, University of California San Diego, La Jolla, CA, United States.
School of Biological Sciences, University of California San Diego, La Jolla, CA, United States.
Front Immunol. 2024 May 10;15:1390263. doi: 10.3389/fimmu.2024.1390263. eCollection 2024.
Cancer immunotherapy, such as immune checkpoint blockade (ICB), has emerged as a groundbreaking approach for effective cancer treatment. Despite its considerable potential, clinical studies have indicated that the current response rate to cancer immunotherapy is suboptimal, primarily attributed to low immunogenicity in certain types of malignant tumors. Immunogenic cell death (ICD) represents a form of regulated cell death (RCD) capable of enhancing tumor immunogenicity and activating tumor-specific innate and adaptive immune responses in immunocompetent hosts. Therefore, gaining a deeper understanding of ICD and its evolution is crucial for developing more effective cancer therapeutic strategies. This review focuses exclusively on both historical and recent discoveries related to ICD modes and their mechanistic insights, particularly within the context of cancer immunotherapy. Our recent findings are also highlighted, revealing a mode of ICD induction facilitated by atypical interferon (IFN)-stimulated genes (ISGs), including polo-like kinase 2 (), during hyperactive type I IFN signaling. The review concludes by discussing the therapeutic potential of ICD, with special attention to its relevance in both preclinical and clinical settings within the field of cancer immunotherapy.
癌症免疫疗法,如免疫检查点阻断(ICB),已成为一种有效的癌症治疗方法。尽管它具有很大的潜力,但临床研究表明,目前癌症免疫疗法的反应率并不理想,主要归因于某些类型的恶性肿瘤的免疫原性较低。免疫原性细胞死亡(ICD)代表一种调节性细胞死亡(RCD)形式,能够增强肿瘤免疫原性,并在免疫活性宿主中激活肿瘤特异性先天和适应性免疫反应。因此,深入了解 ICD 及其演变对于开发更有效的癌症治疗策略至关重要。本综述专门关注与 ICD 模式及其机制见解相关的历史和最新发现,特别是在癌症免疫治疗方面。我们还强调了最近的发现,揭示了在 I 型干扰素信号过度活跃期间,非典型干扰素(IFN)刺激基因(ISGs),包括 Polo 样激酶 2(),促进 ICD 诱导的一种模式。该综述最后讨论了 ICD 的治疗潜力,特别关注其在癌症免疫治疗的临床前和临床环境中的相关性。