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Cancer stem cells and niches: challenges in immunotherapy resistance

Yonglong PanCellular Signaling laboratory, Key laboratory of Molecular Biophysics of MOE, International Research Center for Sensory Biology and Technology of MOST, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074, ChinaChaoyi YuanHepatic Surgery Center, Clinical Medical Research Center of Hepatic Surgery at Hubei Province, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, ChinaChenglong ZengHepatic Surgery Center, Clinical Medical Research Center of Hepatic Surgery at Hubei Province, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, ChinaChaoyang SunNational Clinical Research Center for Obstetrics and Gynecology, Cancer Biology Research Center, Key Laboratory of the MOE, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, ChinaLimin XiaDepartment of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, ChinaGuihua WangHubei Key Laboratory of Hepato-Pancreatic-Biliary Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, ChinaXiaoping ChenHepatic Surgery Center, Clinical Medical Research Center of Hepatic Surgery at Hubei Province, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, ChinaBixiang ZhangHepatic Surgery Center, Clinical Medical Research Center of Hepatic Surgery at Hubei Province, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. [email protected]Jianfeng LiuCellular Signaling laboratory, Key laboratory of Molecular Biophysics of MOE, International Research Center for Sensory Biology and Technology of MOST, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074, China. [email protected]Zeyang DingHepatic Surgery Center, Clinical Medical Research Center of Hepatic Surgery at Hubei Province, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. [email protected]

2025en

ABI

Annotatsiya

Cancer stem cells (CSCs) are central to tumor progression, metastasis, immune evasion, and therapeutic resistance. Characterized by remarkable self-renewal and adaptability, CSCs can transition dynamically between stem-like and differentiated states in response to external stimuli, a process termed "CSC plasticity." This adaptability underpins their resilience to therapies, including immune checkpoint inhibitors and adoptive cell therapies (ACT). Beyond intrinsic properties, CSCs reside in a specialized microenvironment-the CSC niche-which provides immune-privileged protection, sustains their stemness, and fosters immune suppression. This review highlights the critical role of CSCs and their niche in driving immunotherapy resistance, emphasizing the need for integrative approaches to overcome these challenges.

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DOI: 10.1186/s12943-025-02265-2

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