文章：

肿瘤髓系细胞的靶向治疗

Therapeutic targeting of tumour myeloid cells

原文发布日期：2023-02-06

DOI: 10.1038/s41568-022-00546-2

类型: Review Article

开放获取: 否

英文摘要：

Myeloid cells are pivotal within the immunosuppressive tumour microenvironment. The accumulation of tumour-modified myeloid cells derived from monocytes or neutrophils — termed ‘myeloid-derived suppressor cells’ — and tumour-associated macrophages is associated with poor outcome and resistance to treatments such as chemotherapy and immune checkpoint inhibitors. Unfortunately, there has been little success in large-scale clinical trials of myeloid cell modulators, and only a few distinct strategies have been used to target suppressive myeloid cells clinically so far. Preclinical and translational studies have now elucidated specific functions for different myeloid cell subpopulations within the tumour microenvironment, revealing context-specific roles of different myeloid cell populations in disease progression and influencing response to therapy. To improve the success of myeloid cell-targeted therapies, it will be important to target tumour types and patient subsets in which myeloid cells represent the dominant driver of therapy resistance, as well as to determine the most efficacious treatment regimens and combination partners. This Review discusses what we can learn from work with the first generation of myeloid modulators and highlights recent developments in modelling context-specific roles for different myeloid cell subtypes, which can ultimately inform how to drive more successful clinical trials.

摘要翻译： 

髓系细胞在免疫抑制性肿瘤微环境中具有关键作用。来源于单核细胞或中性粒细胞的肿瘤修饰性髓系细胞（称为"髓源性抑制细胞"）及肿瘤相关巨噬细胞的聚集，与不良预后及对化疗、免疫检查点抑制剂等治疗的耐药性相关。遗憾的是，髓系细胞调节剂的大规模临床试验迄今鲜有成功，目前临床上用于靶向抑制性髓系细胞的策略也寥寥无几。临床前及转化研究现已阐明肿瘤微环境中不同髓系细胞亚群的具体功能，揭示了不同髓系细胞群体在疾病进展中的情境特异性作用及其对治疗反应的影响。为提高髓系细胞靶向治疗的成功率，重点在于针对髓系细胞作为耐药性主要驱动因素的肿瘤类型和患者亚群，并确定最有效的治疗方案和联合疗法。本综述探讨了从第一代髓系调节剂工作中可获得的经验，并强调了不同髓系细胞亚型情境特异性作用建模的最新进展，这些成果最终能为推动更成功的临床试验提供参考。

原文链接：

Therapeutic targeting of tumour myeloid cells