肿瘤干细胞的多维度分析：从生物学特性、代谢适应到免疫逃逸机制

作为肿瘤发生、发展、复发和转移的关键因素，肿瘤干细胞（CSCs）的生物学特性、代谢适应和免疫逃逸机制是当前肿瘤学研究的焦点。CSCs具有自我更新、多向分化和肿瘤发生能力，其作用机制可通过克隆进化、层级模型和动态CSCs模型来阐明，其中，动态模型因其更好解释CSCs的起源和功能而被广泛接受。关于CSCs的起源假说涉及细胞-细胞融合、水平基因转移、基因组不稳定性和微环境调控，共同塑造了CSCs的多样性。在分类方面，CSCs包括原发性CSCs（pri-CSCs）、前癌干细胞（pre-CSCs）、迁移性CSCs（mig-CSCs）以及耐化疗-放疗的CSCs（cr-CSCs和rr-CSCs），每一类在肿瘤进展中发挥特定作用。CSCs的表面标志物如CD24、CD34、CD44、CD90、CD133、CD166、EpCAM和LGR5，为识别、分离和靶向CSCs提供了可能，但其表达的不稳定性和异质性增加了治疗难度。CSCs通过代谢重编程适应生存需求，表现出在糖酵解与氧化磷酸化（OXPHOS）之间灵活切换的能力，同时调节氨基酸和脂质代谢。Warburg效应体现了其代谢特征，谷氨酰胺和脂肪酸代谢的改变进一步促进了CSCs的快速增殖与存活。CSCs通过调控代谢网络，维持干性特征、增强抗氧化防御，并适应治疗压力。免疫逃逸是其另一存活策略，CSCs能通过上调PD-L1表达和促进免疫抑制微环境形成有效规避免疫监视。上述特性揭示了CSCs的多维复杂性，强调深入理解其生物学对于开发更有效的肿瘤治疗策略的重要性。未来，靶向CSCs的治疗将聚焦于精准识别表面标志、干预代谢通路以及克服免疫逃逸，以提高癌症治疗的相关性和有效性，最终改善患者预后。

As a key factor in tumorigenesis, progression, recurrence and metastasis, the biological properties, metabolic adaptations and immune escape mechanisms of CSCs are the focus of current oncological research. CSCs possess self-renewal, multidirectional differentiation and tumorigenicity, and their mechanisms of action can be elucidated by the clonal evolution, hierarchical model and the dynamic CSCs model, of which the dynamic model is widely recognized due to its better explanation of the function and origin of CSCs. The origin hypothesis of CSCs involves cell-cell fusion, horizontal gene transfer, genomic instability and microenvironmental regulation, which together shape the diversity of CSCs. In terms of classification, CSCs include primary CSCs (pri-CSCs), precancerous stem cells (pre-CSCs), migratory CSCs (mig-CSCs), and chemo-radiotherapy-resistant CSCs (cr-CSCs and rr-CSCs), with each type playing a specific role in tumor progression. Surface markers of CSCs, such as CD24, CD34, CD44, CD90, CD133, CD166, EpCAM, and LGR5, offer the possibility of identifying, isolating, and targeting CSCs, but the instability and heterogeneity of their expression increase the difficulty of treatment. CSCs have adapted to their survival needs through metabolic reprogramming, showing the ability to flexibly switch between glycolysis and oxidative phosphorylation (OXPHOS), as well as adjustments to amino acid and lipid metabolism. The Warburg effect typifies their metabolic profiles, and altered glutamine and fatty acid metabolism further contributes to the rapid proliferation and survival of CSCs. CSCs are able to maintain their stemness by regulating the metabolic networks to maintain their stemness characteristics, enhance antioxidant defences, and adapt to therapeutic stress. Immune escape is another strategy for CSCs to maintain their survival, and CSCs can effectively evade immune surveillance through mechanisms such as up-regulating PD-L1 expression and promoting the formation of an immunosuppressive microenvironment. Together, these properties reveal the multidimensional complexity of CSCs, underscoring the importance of a deeper understanding of the biology of CSCs for the development of more effective tumor therapeutic strategies. In the future, therapies targeting CSCs will focus on precise identification of surface markers, intervention of metabolic pathways, and overcoming immune escape, with the aim of improving the relevance and efficacy of cancer treatments, and ultimately improving patient prognosis.