CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Targeting MDSCs in cancer: emerging immunotherapeutic and metabolic strategies.
Targeting MDSCs in cancer: emerging immunotherapeutic and metabolic strategies.
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髓源性抑制细胞(MDSCs)是一组异质性未成熟髓系细胞,在肿瘤内建立免疫抑制环境中发挥关键作用。它们通过多种机制阻碍有效的抗肿瘤免疫应答,包括代谢重编程、细胞因子分泌和免疫检查点配体表达。这种免疫抑制活性促进肿瘤进展以及对包括免疫治疗在内的治疗的耐药。近期进展揭示,靶向MDSCs的代谢通路可削弱其抑制功能,为增强抗肿瘤免疫提供了有前景的策略。代谢抑制、直接清除、阻断募集和扩增以及促进分化为成熟免疫细胞等方法正在积极研究中。将这些策略与免疫检查点抑制剂和基于细胞的疗法(如癌症疫苗和过继性T细胞或NK细胞疗法)相结合,在克服免疫耐药方面具有巨大潜力。
然而,MDSCs异质性、毒性和生物标志物验证等挑战仍需解决,以优化临床转化。本综述全面涵盖了目前对肿瘤微环境中MDSC介导免疫抑制的免疫代谢机制的认识。它探讨了旨在通过代谢干预、清除以及调节其募集和分化来靶向MDSCs的新兴治疗策略。
此外,还讨论了将MDSC靶向方法与现有免疫疗法相结合,重点介绍了正在进行的临床试验,并评估了未来方向,如个性化、生物标志物驱动的治疗。最终,本综述强调了以MDSC为靶点的疗法在显著提高癌症免疫治疗疗效和克服肿瘤免疫逃逸机制方面的潜力。
Myeloid-derived suppressor cells (MDSCs) are a diverse group of immature myeloid cells critically involved in establishing an immunosuppressive environment within tumors. They impede effective anti-tumor immune responses through multiple mechanisms, including metabolic reprogramming, cytokine secretion, and immune checkpoint ligand expression. This immunosuppressive activity enables tumor progression and resistance to therapies, including immunotherapy. Recent advances reveal that targeting the metabolic pathways of MDSCs can impair their suppressive functions, offering promising strategies to enhance anti-cancer immunity. Approaches such as metabolic inhibition, direct depletion, blockade of recruitment and expansion, and promotion of differentiation into mature immune cells are under active investigation.
Combining these strategies with immune checkpoint inhibitors and cell-based therapies, such as cancer vaccines and adoptive T-cell or NK-cell therapies, holds significant potential for overcoming immune resistance. Nonetheless, challenges including MDSC heterogeneity, toxicity, and biomarker validation must be addressed to optimize clinical translation.
This review comprehensively covers current insights into the immune-metabolic mechanisms underpinning MDSC-mediated immunosuppression in the tumor microenvironment. It explores emerging therapeutic strategies aimed at targeting MDSCs through metabolic interventions, depletion, and modulation of their recruitment and differentiation.
Furthermore, it discusses the integration of MDSC-targeted approaches with existing immunotherapies, highlights ongoing clinical trials, and assesses future directions, such as personalized, biomarker-driven treatments. Ultimately, this review underscores the potential of MDSC-focused therapies to significantly improve the efficacy of cancer immunotherapy and overcome mechanisms of tumor immune evasion.
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