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Cancer stem cells and niches: challenges in immunotherapy resistance

Yonglong Pan, Chaoyi Yuan, Chenglong Zeng, Chaoyang Sun, Limin Xia, Guihua Wang, Xiaoping Chen, Bixiang Zhang, Jianfeng Liu, Zeyang Ding

2025Molecular Cancer77 citationsDOIOpen Access PDF

Abstract

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.

Topics & Concepts

BiologyCancerImmunotherapyResistance (ecology)Stem cellCancer researchCancer stem cellNicheCancer immunotherapyGeneticsEcologyCancer Cells and MetastasisImmunotherapy and Immune ResponsesCancer Immunotherapy and Biomarkers
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