Cell Stress & Immunity (CSI) Lab, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium.
Laboratory of Experimental Oncology, Department of Oncology, Leuven Cancer Institute, KU Leuven, Leuven, Belgium.
Oncoimmunology. 2023 Jun 3;12(1):2219591. doi: 10.1080/2162402X.2023.2219591. eCollection 2023.
Immunogenic cell death (ICD) refers to an immunologically distinct process of regulated cell death that activates, rather than suppresses, innate and adaptive immune responses. Such responses culminate into T cell-driven immunity against antigens derived from dying cancer cells. The potency of ICD is dependent on the immunogenicity of dying cells as defined by the antigenicity of these cells and their ability to expose immunostimulatory molecules like damage-associated molecular patterns (DAMPs) and cytokines like type I interferons (IFNs). Moreover, it is crucial that the host's immune system can adequately detect the antigenicity and adjuvanticity of these dying cells. Over the years, several well-known chemotherapies have been validated as potent ICD inducers, including (but not limited to) anthracyclines, paclitaxels, and oxaliplatin. Such ICD-inducing chemotherapeutic drugs can serve as important combinatorial partners for anti-cancer immunotherapies against highly immuno-resistant tumors. In this Trial Watch, we describe current trends in the preclinical and clinical integration of ICD-inducing chemotherapy in the existing immuno-oncological paradigms.
免疫原性细胞死亡(ICD)是一种受调控的细胞死亡过程,具有独特的免疫学特征,能够激活而非抑制固有和适应性免疫反应。这种反应最终导致针对源自死亡癌细胞的抗原的 T 细胞驱动的免疫。ICD 的效力取决于死亡细胞的免疫原性,这取决于这些细胞的抗原性及其暴露免疫刺激性分子(如损伤相关分子模式(DAMPs)和细胞因子,如 I 型干扰素(IFNs))的能力。此外,宿主的免疫系统能够充分检测这些死亡细胞的抗原性和佐剂性至关重要。多年来,已有几种著名的化疗药物被验证为有效的 ICD 诱导剂,包括(但不限于)蒽环类药物、紫杉醇和奥沙利铂。这种 ICD 诱导化疗药物可以作为针对高度免疫抵抗性肿瘤的抗癌免疫治疗的重要组合伙伴。在本次试验观察中,我们描述了在现有的免疫肿瘤学范例中,ICD 诱导化疗在临床前和临床整合方面的当前趋势。