RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Myeloid-Derived Suppressor Cells in Cancer: Mechanistic Insights and Targeted Therapeutic Innovations.
Myeloid-Derived Suppressor Cells in Cancer: Mechanistic Insights and Targeted Therapeutic Innovations.
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髓源性抑制细胞(MDSCs)是一群异质性的未成熟髓系细胞,在癌症中异常扩增,并表现出强效的免疫抑制特性。它们通过免疫学和非免疫学机制促进肿瘤进展。在免疫学方面,MDSCs通过抑制T细胞和NK细胞等效应细胞来抑制抗肿瘤反应,促进免疫逃逸。在非免疫学方面,它们通过上皮-间充质转化、血管生成和转移前生态位形成等过程促进肿瘤生长和转移。MDSC的积聚与肿瘤加速进展密切相关,包括对免疫治疗和常规治疗的耐药,使这些细胞成为关键的治疗靶点。临床研究已证明MDSC靶向策略具有提高治疗疗效的潜力。
然而,在实现MDSC靶向治疗的特异性和有效性方面仍存在挑战,强调需要对其生物学有更深入的了解。本综述总结了MDSCs的起源、分类和生物学特征、其在肿瘤进展中的双重作用及其临床意义。
我们还讨论了临床和临床前研究的最新进展,包括传统靶向治疗和新兴创新策略。通过整合当前研究结果,我们旨在提供关于MDSCs在癌症中作用的全面视角,并为推进癌症治疗和药物开发提供有价值的见解。
Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature myeloid cells that expand aberrantly in cancer and exhibit potent immunosuppressive properties. They contribute to tumor progression through both immunological and nonimmunological mechanisms. Immunologically, MDSCs suppress antitumor responses by inhibiting effector cells such as T cells and NK cells, facilitating immune evasion.
Nonimmunologically, they promote tumor growth and metastasis through processes such as the epithelial‒mesenchymal transition, angiogenesis, and premetastatic niche formation. MDSC accumulation is closely linked to accelerated tumor progression, including resistance to both immunotherapies and conventional treatments, making these cells critical therapeutic targets. Clinical studies have demonstrated the potential of MDSC-targeted strategies to improve treatment efficacy.
However, challenges remain in achieving specificity and effectiveness in MDSC-targeted therapies, emphasizing the need for a deeper understanding of their biology. This review summarizes the origin, classification, and biological characteristics of MDSCs, their dual roles in tumor progression, and their clinical significance.
We also discuss recent advances in clinical and preclinical studies, including both traditional targeted therapies and emerging innovative strategies. By integrating current findings, we aim to provide a comprehensive perspective on the role of MDSCs in cancer and valuable insights for advancing cancer treatment and drug development.
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