文章：

工程化髓系细胞在肿瘤微环境中的治疗效用

Therapeutic utility of engineered myeloid cells in the tumor microenvironment 

原文发布日期：2023-02-28 

英文摘要：

Despite promising results shown in hematologic tumors, immunotherapies for the treatment of solid tumors have mostly failed so far. The immunosuppressive tumor microenvironment and phenotype of tumor infiltrating macrophages are among the more prevalent reasons for this failure. Tumor associated macrophages (TAMs, M2-macrophages) are circulating myeloid cells recruited to the local tumor microenvironment, and together with regulatory T cells (T-regs), are reprogrammed to become immune suppressive. This results in the inactivation or hampered recruitment of cytotoxic CD8 + T and Natural Killer (NK) cells. Recently, attempts have been made to try to leverage specific myeloid functions and properties, including their ability to reach the TME and to mediate the phagocytosis of cancer cells. Additionally, myeloid cells have been used for drug delivery and reprogramming the tumor microenvironment in cancer patients. This approach, together with the advancements in genome editing, paved the way for the development of novel cell-mediated immunotherapies. This article focuses on the latest studies that detail the therapeutic properties of genetically engineered or pharmacologically modulated myeloid cells in cancer preclinical models, limitations, pitfalls, and evaluations of these approaches in patients with cancer. 

摘要翻译： 

尽管在血液肿瘤中展现出前景良好的疗效，免疫疗法在实体瘤治疗领域迄今大多未能取得成功。免疫抑制性肿瘤微环境及肿瘤浸润巨噬细胞的表型是导致此类失败的主要原因之一。肿瘤相关巨噬细胞（TAMs，即M2型巨噬细胞）作为循环髓系细胞被招募至局部肿瘤微环境，与调节性T细胞（T-regs）共同被重编程为免疫抑制状态，从而导致细胞毒性CD8 + T细胞和自然杀伤（NK）细胞失活或招募受阻。近期研究尝试利用髓系细胞的特定功能与特性——包括其抵达肿瘤微环境的能力及介导癌细胞吞噬的作用，同时探索髓系细胞在癌症患者药物递送和肿瘤微环境重编程中的应用。这一策略结合基因组编辑技术的进步，为开发新型细胞介导的免疫疗法开辟了道路。本文重点综述最新研究，详细探讨基因工程改造或药理调控的髓系细胞在癌症临床前模型中的治疗特性、现有局限性及潜在缺陷，并对这些策略在癌症患者中的临床应用价值进行评估。

原文链接：

Therapeutic utility of engineered myeloid cells in the tumor microenvironment