The Second Hospital of Jilin University, Changchun, China.
Department of Hepatobiliary and Pancreatic Surgery, Second Hospital of Jilin University, Changchun, China.
Aging (Albany NY). 2024 May 23;16(11):10165-10196. doi: 10.18632/aging.205858.
Currently, antitumor drugs show limited clinical outcomes, mainly due to adaptive resistance. Clinical evidence has highlighted the importance of the tumor microenvironment (TME) and tumor-associated macrophages (TAMs) in tumor response to conventional antitumor drugs. Preclinical studies show that TAMs following antitumor agent can be reprogrammed to an immunosuppressive phenotype and proangiogenic activities through different mechanisms, mediating drug resistance and poor prognosis. Potential extrinsic inhibitors targeting TAMs repolarize to an M1-like phenotype or downregulate proangiogenic function, enhancing therapeutic efficacy of anti-tumor therapy. Moreover, pharmacological modulation of macrophages that restore the immune stimulatory characteristics is useful to reshaping the tumor microenvironment, thus further limiting tumor growth. This review aims to introduce macrophage response in tumor therapy and provide a potential therapeutic combination strategy of TAM-targeting immunomodulation with conventional antitumor drugs.
目前，抗肿瘤药物的临床疗效有限，主要是由于适应性耐药。临床证据强调了肿瘤微环境（TME）和肿瘤相关巨噬细胞（TAMs）在肿瘤对传统抗肿瘤药物反应中的重要性。临床前研究表明，抗肿瘤药物治疗后的 TAMs 可以通过不同的机制重新编程为具有免疫抑制表型和促血管生成活性，介导耐药性和预后不良。针对 TAMs 的潜在外在抑制剂可以使其重新极化为 M1 样表型或下调促血管生成功能，从而增强抗肿瘤治疗的疗效。此外，恢复免疫刺激特征的巨噬细胞的药理学调节有助于重塑肿瘤微环境，从而进一步限制肿瘤生长。本综述旨在介绍肿瘤治疗中巨噬细胞的反应，并提供一种针对 TAM 的免疫调节与传统抗肿瘤药物相结合的潜在治疗策略。
