免疫检查点抑制剂 （ICIs）用于固体肿瘤的治疗，在临床实践中引入后戏剧性地改变了局面。然而，ICIs治疗中有多达70％的患者对治疗无反应。传统上，大多数免疫疗法的方法旨在直接刺激抗肿瘤T细胞反应。最近，肿瘤相关巨噬细胞因其在实体瘤中的主导地位而变得越来越重要。它们与肿瘤细胞以及肿瘤微环境中的免疫和基质细胞之间的密集交流可以促进肿瘤生成或抑制肿瘤生成的巨噬细胞表型。反过来，肿瘤相关巨噬细胞在肿瘤微环境中强烈塑造细胞因子和代谢物水平，因此是反肿瘤免疫中的中心作用者。因此，存在着具有双重属性的巨噬细胞群体，这提高了增强或减弱它们功能的治疗可能性。然而，控制肿瘤相关巨噬细胞极化的分子信号尚不完全了解。深入了解单核细胞/巨噬细胞在循环和不同肿瘤微环境中的特性将（i）允许开发新的治疗方法，以及（ii）可以进一步帮助我们了解限制当前治疗的潜在机制，以增加疗效的组合疗法。在本次回顾中，我们总结了有关肿瘤相关巨噬细胞群体的异质性的最新数据，并讨论了使用已知分子途径定向巨噬细胞的策略，具有直接的临床应用潜力。版权所有 © 2022 The Authors. 由Elsevier Ltd.出版。保留所有权利。

The introduction of immune checkpoint inhibitors (ICIs) for the treatment of solid cancers dramatically turned the tables in clinical routine. However, therapy success is still limited with up to 70% of non-responders in patients with ICI treatment. Traditionally, most immunotherapy approaches aim at directly stimulating anti-tumor T cell responses. More recently, tumor-associated macrophages have come into focus due to their predominance in solid tumors. Intensive cross-talk with tumor cells and immune as well as stromal cells within the tumor microenvironment can drive either pro- or anti-tumorigenic macrophage phenotypes. In turn, tumor-associated macrophages strongly shape cytokine and metabolite levels in the tumor microenvironment and thus are central players in anti-tumor immunity. Thus, ambivalent macrophage populations exist which raises therapeutic possibilities to either enhance or diminish their functionality. However, molecular signals controlling tumor-associated macrophage polarization are incompletely understood. Gaining in-depth understanding of monocyte/macrophage properties both in circulation and within distinct tumor microenvironments would (i) allow the development of new therapeutic approaches, and (ii) could additionally aid our understanding of underlying mechanisms limiting current therapy with the option of combinatorial therapies to increase efficacy. In this review, we summarize recent data addressing heterogeneity of tumor-associated macrophage populations and we discuss strategies to target macrophages using known molecular pathways with the potential for straight-forward clinical application.Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.