Immunogenic dying cells elicit potent anti-tumor T cell immunity against lung metastasis and tumorigenesis

Abstract Purpose 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 imm...

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Main Authors: Min Hu, Xinyu Meng, Tong Wang, Yifan Wang, Xiaodong Chen, Dongliang Xu, Wei He, Hongjia Zhang, Wenzheng Guo, Bo Jing, Siwei Zhang, Jianhua Xu, Beibei Sun, Xueqian Sun, Tingting Liu, Na Ni, Tongtong Zhang, Wenwen Cui, Xiaoyu Wu, Liping Xia, Feng Yao, Fang Zhang, Jing Du, Jiong Deng
Format: Article
Language:English
Published: Springer 2025-01-01
Series:Journal of Cancer Research and Clinical Oncology
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Online Access:https://doi.org/10.1007/s00432-025-06087-z
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author Min Hu
Xinyu Meng
Tong Wang
Yifan Wang
Xiaodong Chen
Dongliang Xu
Wei He
Hongjia Zhang
Wenzheng Guo
Bo Jing
Siwei Zhang
Jianhua Xu
Beibei Sun
Xueqian Sun
Tingting Liu
Na Ni
Tongtong Zhang
Wenwen Cui
Xiaoyu Wu
Liping Xia
Feng Yao
Fang Zhang
Jing Du
Jiong Deng
author_facet Min Hu
Xinyu Meng
Tong Wang
Yifan Wang
Xiaodong Chen
Dongliang Xu
Wei He
Hongjia Zhang
Wenzheng Guo
Bo Jing
Siwei Zhang
Jianhua Xu
Beibei Sun
Xueqian Sun
Tingting Liu
Na Ni
Tongtong Zhang
Wenwen Cui
Xiaoyu Wu
Liping Xia
Feng Yao
Fang Zhang
Jing Du
Jiong Deng
author_sort Min Hu
collection DOAJ
description Abstract Purpose 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. Methods 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. Results 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. Conclusion Immunization with the ICD dying tumor cells evokes potent tumor-specific T cell immunity, which provides a novel approach for cancer immunotherapy.
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publisher Springer
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series Journal of Cancer Research and Clinical Oncology
spelling doaj-art-29400e8f2a6e484fa91e3cc6e2df33962025-02-09T12:10:32ZengSpringerJournal of Cancer Research and Clinical Oncology1432-13352025-01-01151111110.1007/s00432-025-06087-zImmunogenic dying cells elicit potent anti-tumor T cell immunity against lung metastasis and tumorigenesisMin Hu0Xinyu Meng1Tong Wang2Yifan Wang3Xiaodong Chen4Dongliang Xu5Wei He6Hongjia Zhang7Wenzheng Guo8Bo Jing9Siwei Zhang10Jianhua Xu11Beibei Sun12Xueqian Sun13Tingting Liu14Na Ni15Tongtong Zhang16Wenwen Cui17Xiaoyu Wu18Liping Xia19Feng Yao20Fang Zhang21Jing Du22Jiong Deng23Department of Laboratory Medicine, Shanghai East Hospital, Tongji University School of MedicineMedical Research Center, Binzhou Medical University HospitalDepartment of Physiology, School of Basic Medical Sciences, Shandong Second Medical UniversityCancer Institute of Integrative Medicine, Zhejiang Key Laboratory of Cancer Prevention and Therapy Combining Traditional Chinese and Western Medicine, Zhejiang Academy of Traditional Chinese Medicine, Tongde Hospital of Zhejiang ProvinceDepartment of Radiation Oncology, Yantai Affiliated Hospital of Binzhou Medical UniversityKey Laboratory of Cell Differentiation and Apoptosis of Chinese Minister of Education, Department of Pathophysiology, Shanghai Jiao Tong University School of MedicineKey Laboratory of Cell Differentiation and Apoptosis of Chinese Minister of Education, Department of Pathophysiology, Shanghai Jiao Tong University School of MedicineKey Laboratory of Cell Differentiation and Apoptosis of Chinese Minister of Education, Department of Pathophysiology, Shanghai Jiao Tong University School of MedicineDepartment of Laboratory Medicine, Shanghai East Hospital, Tongji University School of MedicineDepartment of Laboratory Medicine, Shanghai Pulmonary Hospital Affiliated Tongji UniversityKey Laboratory of Cell Differentiation and Apoptosis of Chinese Minister of Education, Department of Pathophysiology, Shanghai Jiao Tong University School of MedicineDepartment of Laboratory Medicine, Shanghai Pulmonary Hospital Affiliated Tongji UniversityDepartment of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong UniversityMedical Research Center, Binzhou Medical University HospitalMedical Research Center, Binzhou Medical University HospitalMedical Research Center, Binzhou Medical University HospitalDepartment of Radiation Oncology, Yantai Affiliated Hospital of Binzhou Medical UniversityDepartment of Physiology, School of Basic Medical Sciences, Shandong Second Medical UniversityDepartment of Physiology, School of Basic Medical Sciences, Shandong Second Medical UniversityMedical Research Center, Binzhou Medical University HospitalDepartment of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong UniversityDepartment of Radiation Oncology, Yantai Affiliated Hospital of Binzhou Medical UniversityMedical Research Center, Binzhou Medical University HospitalMedical Research Center, Binzhou Medical University HospitalAbstract Purpose 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. Methods 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. Results 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. Conclusion Immunization with the ICD dying tumor cells evokes potent tumor-specific T cell immunity, which provides a novel approach for cancer immunotherapy.https://doi.org/10.1007/s00432-025-06087-zLung metastasisImmunogenic cell deathLung tumorigenesisT cell immunityTumor vaccine
spellingShingle Min Hu
Xinyu Meng
Tong Wang
Yifan Wang
Xiaodong Chen
Dongliang Xu
Wei He
Hongjia Zhang
Wenzheng Guo
Bo Jing
Siwei Zhang
Jianhua Xu
Beibei Sun
Xueqian Sun
Tingting Liu
Na Ni
Tongtong Zhang
Wenwen Cui
Xiaoyu Wu
Liping Xia
Feng Yao
Fang Zhang
Jing Du
Jiong Deng
Immunogenic dying cells elicit potent anti-tumor T cell immunity against lung metastasis and tumorigenesis
Journal of Cancer Research and Clinical Oncology
Lung metastasis
Immunogenic cell death
Lung tumorigenesis
T cell immunity
Tumor vaccine
title Immunogenic dying cells elicit potent anti-tumor T cell immunity against lung metastasis and tumorigenesis
title_full Immunogenic dying cells elicit potent anti-tumor T cell immunity against lung metastasis and tumorigenesis
title_fullStr Immunogenic dying cells elicit potent anti-tumor T cell immunity against lung metastasis and tumorigenesis
title_full_unstemmed Immunogenic dying cells elicit potent anti-tumor T cell immunity against lung metastasis and tumorigenesis
title_short Immunogenic dying cells elicit potent anti-tumor T cell immunity against lung metastasis and tumorigenesis
title_sort immunogenic dying cells elicit potent anti tumor t cell immunity against lung metastasis and tumorigenesis
topic Lung metastasis
Immunogenic cell death
Lung tumorigenesis
T cell immunity
Tumor vaccine
url https://doi.org/10.1007/s00432-025-06087-z
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