Department of Radiation Oncology, Weill Cornell Medical College, New York, New York, USA.
Tumor Stroma Interactions, Department of Cancer Research, Luxembourg Institute of Health, Luxembourg, Luxembourg.
Immunol Rev. 2024 Jan;321(1):20-32. doi: 10.1111/imr.13271. Epub 2023 Sep 7.
Cancer cells undergoing immunogenic cell death (ICD) can initiate adaptive immune responses against dead cell-associated antigens, provided that (1) said antigens are not perfectly covered by central tolerance (antigenicity), (2) cell death occurs along with the emission of immunostimulatory cytokines and damage-associated molecular patterns (DAMPs) that actively engage immune effector mechanisms (adjuvanticity), and (3) the microenvironment of dying cells is permissive for the initiation of adaptive immunity. Finally, ICD-driven immune responses can only operate and exert cytotoxic effector functions if the microenvironment of target cancer cells enables immune cell infiltration and activity. Multiple forms of radiation, including non-ionizing (ultraviolet) and ionizing radiation, elicit bona fide ICD as they increase both the antigenicity and adjuvanticity of dying cancer cells. Here, we review the molecular determinants of ICD as elicited by radiation as we critically discuss strategies to reinforce the immunogenicity of cancer cells succumbing to clinically available radiation strategies.
发生免疫原性细胞死亡 (ICD) 的癌细胞可以引发针对死细胞相关抗原的适应性免疫反应，前提是 (1) 这些抗原没有被中枢耐受 (抗原性) 完全覆盖，(2) 细胞死亡伴随着免疫刺激细胞因子和损伤相关分子模式 (DAMPs) 的释放，这些细胞因子和 DAMPs 积极参与免疫效应机制 (佐剂活性)，以及 (3) 死亡细胞的微环境允许适应性免疫的启动。最后，如果靶癌细胞的微环境允许免疫细胞浸润和活性，ICD 驱动的免疫反应才能发挥作用并发挥细胞毒性效应功能。包括非电离 (紫外线) 和电离辐射在内的多种形式的辐射通过增加垂死癌细胞的抗原性和佐剂活性，引发真正的 ICD。在这里，我们回顾了辐射引发的 ICD 的分子决定因素，并批判性地讨论了增强对临床可用辐射策略屈服的癌细胞免疫原性的策略。
