CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Leveraging macrophage plasticity for precision-targeted tumor immunotherapy.
Leveraging macrophage plasticity for precision-targeted tumor immunotherapy.
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尽管免疫治疗在某些恶性肿瘤中展现出显著的治疗潜力,但其整体临床疗效仍不理想。新出现的证据表明,肿瘤微环境(TME)在决定免疫治疗反应中发挥关键作用,而肿瘤相关巨噬细胞(TAMs)——TME中占主导地位的免疫细胞群体——与不良预后、转移进展和治疗耐药密切相关。传统上,巨噬细胞被分为两种主要活化状态:促炎M1(经典活化)表型和抗炎M2(替代活化)表型。然而,这种二元分类系统未能完全反映TAMs的功能复杂性和表型可塑性。这篇综合性综述批判性地审视了TAM异质性,并探讨了超越传统M1/M2二分法的新兴亚型分类范式。此外,我们系统性地考察了三种主要治疗策略:招募抑制、TAM清除和表型重编程,强调其与现有免疫疗法的协同潜力。这些多方面的策略为开发联合疗法以克服当前癌症治疗的局限性提供了新的见解。
While immunotherapy has demonstrated remarkable therapeutic potential in certain malignancies, its overall clinical efficacy remains suboptimal. Emerging evidence indicates that the tumor microenvironment (TME) plays a pivotal role in determining immunotherapy response, with tumor-associated macrophages (TAMs) - the predominant immune cell population within TME - being closely associated with poor prognosis, metastatic progression, and therapeutic resistance.
Traditionally, macrophages are classified into two primary activation states: the pro-inflammatory M1 (classically activated) phenotype and the anti-inflammatory M2 (alternatively activated) phenotype.
However, this binary classification system fails to fully capture the functional complexity and phenotypic plasticity of TAMs. This comprehensive review critically examines TAM heterogeneity and explores emerging subtyping paradigms beyond conventional M1/M2 dichotomization.
Furthermore, we systematically examine three principal therapeutic strategies: recruitment inhibition, TAM depletion, and phenotypic reprogramming, emphasizing their synergistic potential with existing immunotherapies. These multifaceted approaches provide novel insights for developing combination therapies to overcome current limitations in cancer treatment.
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