Hu Min, Meng Xinyu, Wang Tong, Wang Yifan, Chen Xiaodong, Xu Dongliang, He Wei, Zhang Hongjia, Guo Wenzheng, Jing Bo, Zhang Siwei, Xu Jianhua, Sun Beibei, Sun Xueqian, Liu Tingting, Ni Na, Zhang Tongtong, Cui Wenwen, Wu Xiaoyu, Xia Liping, Yao Feng, Zhang Fang, Du Jing, Deng Jiong
Department of Laboratory Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200123, China.
Medical Research Center, Binzhou Medical University Hospital, Binzhou, Shandong, 256600, P.R. China.
J Cancer Res Clin Oncol. 2025 Jan 18;151(1):38. doi: 10.1007/s00432-025-06087-z.
Immune checkpoint blockades (ICBs) are promising, however they do not fit all types of tumor, such as those lack of tumor antigens. Induction of potent anti-tumor T cell immunity is critical for cancer therapy. In this study, we investigated the efficacy of immunotherapy via the immunogenic cell death (ICD) dying tumor cells in mouse models of lung metastasis and tumorigenesis.
ICD was induced by short exposure to lethal dose of chemotherapeutic drug doxorubicin (Dox), which initiated an irreversible ICD program in tumor cells. We immunized mice with ICD dying tumor cells in prevention, therapy in lung metastasis models, and Gprc5a-knockout (ko) model of lung tumorigenesis. T cells and macrophages isolated from lymph nodes or tumor tissues were analyzed by flow cytometry. Cytokines were analyzed by ELISA or Q-PCR analysis.
Immunization with these live but ICD dying tumor cells induced potent tumor-specific anti-tumor T cell immunity, which not only protected host from challenge by these tumor cells in prevention and therapy in mouse model of lung metastasis, but also prevented tumors development in Gprc5a-ko mouse model of lung tumorigenesis. The lymphocytes from lymph nodes and tumor tissues exhibited greatly enhanced activities of Th1 cells and M1 macrophages.
Immunization with the ICD dying tumor cells evokes potent tumor-specific T cell immunity, which provides a novel approach for cancer immunotherapy.
免疫检查点阻断疗法前景广阔，但并不适用于所有类型的肿瘤，比如那些缺乏肿瘤抗原的肿瘤。诱导强大的抗肿瘤T细胞免疫对于癌症治疗至关重要。在本研究中，我们在肺转移和肿瘤发生的小鼠模型中，研究了通过免疫原性细胞死亡（ICD）的死亡肿瘤细胞进行免疫治疗的效果。
通过短时间暴露于致死剂量的化疗药物阿霉素（Dox）诱导ICD，这会在肿瘤细胞中启动不可逆的ICD程序。我们在预防、肺转移模型的治疗以及肺肿瘤发生的Gprc5a基因敲除（ko）模型中，用ICD死亡的肿瘤细胞免疫小鼠。通过流式细胞术分析从淋巴结或肿瘤组织中分离出的T细胞和巨噬细胞。通过ELISA或Q-PCR分析细胞因子。
用这些存活但处于ICD状态的死亡肿瘤细胞进行免疫，可诱导强大的肿瘤特异性抗肿瘤T细胞免疫，这不仅在肺转移小鼠模型的预防和治疗中保护宿主免受这些肿瘤细胞的攻击，还能在肺肿瘤发生的Gprc5a-ko小鼠模型中预防肿瘤发展。来自淋巴结和肿瘤组织的淋巴细胞表现出Th1细胞和M1巨噬细胞的活性大大增强。
用ICD死亡的肿瘤细胞进行免疫可引发强大的肿瘤特异性T细胞免疫，这为癌症免疫治疗提供了一种新方法。
