Department of Pathology and Immunology, University of Geneva, Geneva, Switzerland.
Ludwig Institute for Cancer Research, Lausanne, Switzerland.
Nat Rev Clin Oncol. 2022 Jun;19(6):402-421. doi: 10.1038/s41571-022-00620-6. Epub 2022 Mar 30.
In the past decade, substantial advances have been made in understanding the biology of tumour-associated macrophages (TAMs), and their clinical relevance is emerging. A particular aspect that is becoming increasingly clear is that the interaction of TAMs with cancer cells and stromal cells in the tumour microenvironment enables and sustains most of the hallmarks of cancer. Therefore, manipulation of TAMs could enable improved disease control in a substantial fraction of patients across a large number of cancer types. In this Review, we examine the diversity of TAMs in various cancer indications and how this heterogeneity is being revisited with the advent of single-cell technologies, and then explore the current knowledge on the functional roles of different TAM states and the prognostic and predictive value of TAM-related signatures. We also review agents targeting TAMs that are currently being or will soon be tested in clinical trials, and how manipulations of TAMs can improve existing anticancer treatments. Finally, we discuss how TAM-targeting approaches could be further integrated into routine clinical practice, considering a precision oncology approach and viewing TAMs as a dynamic population that can evolve under treatment pressure.
在过去的十年中，人们对肿瘤相关巨噬细胞（TAMs）的生物学特性有了深入的了解，其临床相关性也逐渐显现出来。一个越来越明显的方面是，TAMs 与肿瘤微环境中的癌细胞和基质细胞的相互作用，使癌症的大多数特征得以维持和发展。因此，对 TAMs 的干预可能会使大量癌症类型中的大部分患者的疾病得到更好的控制。在这篇综述中，我们研究了不同癌症类型中 TAMs 的多样性，以及单细胞技术的出现如何重新审视这种异质性，然后探讨了不同 TAM 状态的功能作用以及 TAM 相关特征的预后和预测价值的现有知识。我们还回顾了目前正在或即将在临床试验中测试的针对 TAMs 的药物，以及对 TAMs 的干预如何改善现有的抗癌治疗方法。最后，我们讨论了如何进一步将 TAM 靶向方法整合到常规临床实践中，考虑到精准肿瘤学的方法，并将 TAMs 视为一个可以在治疗压力下演变的动态群体。
