肿瘤相关巨噬细胞（TAM）是免疫抑制肿瘤微环境（TME）中的主要细胞浸润。 TAM 对于促进促炎条件、肿瘤生长、转移和抑制治疗反应至关重要。许多癌症患者天生对化疗耐药，或者在初始治疗后产生耐药性。 TME 中的 TAM 水平与化疗耐药性之间存在临床相关性。因此，TAM 在导致化疗耐药性方面的关键作用引起了人们对靶向 TAM 来逆转这种耐药性的极大关注。这种方法的先决条件是彻底了解 TAM 抑制化疗药物反应的各种潜在机制。这些机制包括增强药物流出、调节药物代谢和解毒、支持癌症干细胞 (CSC) 抵抗、促进上皮间质转化 (EMT)、抑制药物渗透及其代谢、刺激血管生成、影响抑制性 STAT3/NF-κB 生存途径，并释放特异性抑制性细胞因子，包括 TGF-β 和 IL-10。因此，已经开发了几种策略来克服 TAM 调节的化学耐药性。其中包括旨在耗尽 TAM、将其重新极化为抗肿瘤 M1 样表型或阻止单核细胞募集至 TME 的新疗法。目前 TAM 靶向治疗的结果并不理想。然而，联合使用 TAM 靶向疗法似乎很有前景，其中包括针对 TAM 的放疗、化疗、趋化因子受体抑制剂、免疫疗法和负载纳米颗粒。讨论了这些策略的临床局限性。

Tumor-associated macrophages (TAMs) are the predominant cell infiltrate in the immunosuppressive tumor microenvironment (TME). TAMs are central to fostering pro-inflammatory conditions, tumor growth, metastasis, and inhibiting therapy responses. Many cancer patients are innately refractory to chemotherapy and or develop resistance following initial treatments. There is a clinical correlation between the level of TAMs in the TME and chemoresistance. Hence, the pivotal role of TAMs in contributing to chemoresistance has garnered significant attention toward targeting TAMs to reverse this resistance. A prerequisite for such an approach requires a thorough understanding of the various underlying mechanisms by which TAMs inhibit response to chemotherapeutic drugs. Such mechanisms include enhancing drug efflux, regulating drug metabolism and detoxification, supporting cancer stem cell (CSCs) resistance, promoting epithelial-mesenchymal transition (EMT), inhibiting drug penetration and its metabolism, stimulating angiogenesis, impacting inhibitory STAT3/NF-κB survival pathways, and releasing specific inhibitory cytokines including TGF-β and IL-10. Accordingly, several strategies have been developed to overcome TAM-modulated chemoresistance. These include novel therapies that aim to deplete TAMs, repolarize them toward the anti-tumor M1-like phenotype, or block recruitment of monocytes into the TME. Current results from TAM-targeted treatments have been unimpressive; however, the use of TAM-targeted therapies in combination appears promising These include targeting TAMs with radiotherapy, chemotherapy, chemokine receptor inhibitors, immunotherapy, and loaded nanoparticles. The clinical limitations of these strategies are discussed.