Today, science and medicine are striving to develop novel techniques for treating deadly diseases, including a wide range of cancers. Efforts are being made to better understand the molecular and biochemical mechanisms of tumor cell functioning, but a particular emphasis has recently been given to investigating immune cells residing in the tumor microenvironment, which may lead to revolutionary benefits in the design of new immunotherapies. Among these cells, tumor-associated macrophages (TAMs) are highly abundant and act as critical regulators of ovarian cancer progression, metastasis, and resistance to therapy. Their dual nature—as drivers of malignancy and as potential therapeutic mediators—has positioned them at the forefront of research into next-generation immunotherapies. As therapeutic targets, approaches include blocking macrophage recruitment (e.g., CSF-1/CSF-1R inhibitors), selectively depleting subsets of TAMs (e.g., via Folate Receptor Beta), or reprogramming immunosuppressive M2-like macrophages toward an anti-tumor M1 phenotype. On the other hand, macrophages can also serve as a therapeutic tool—they may be engineered to enhance anti-tumor immunity, as exemplified by the development of Chimeric Antigen Receptor Macrophages (CAR-Ms), or leveraged as delivery vehicles for targeted drug transport into the tumor microenvironment. A particularly innovative strategy involves Macrophage–Drug Conjugates (MDCs), which employs the transfer of iron-binding proteins (TRAIN) mechanism for precise intracellular delivery of therapeutic agents, thereby enhancing drug efficacy while minimizing systemic toxicity. This review integrates current knowledge of TAM biology, highlights emerging therapeutic approaches, and underscores the promise of macrophage-based interventions in ovarian cancer. By integrating macrophage-targeting strategies with advanced immunotherapeutic platforms, novel treatment paradigms may be determined that could substantially improve outcomes for patients with ovarian cancer and other solid tumors. Our work highlights that macrophages should be a particular area of research interest in the context of cancer treatment.
当前，科学与医学正致力于开发治疗致命性疾病（包括多种癌症）的新技术。研究者们正努力深入理解肿瘤细胞功能的分子与生化机制，但近期研究重点已转向探索肿瘤微环境中的免疫细胞，这可能为新型免疫疗法的设计带来革命性突破。在这些细胞中，肿瘤相关巨噬细胞（TAMs）数量丰富，是调控卵巢癌进展、转移及治疗耐药的关键调节因子。其双重特性——既可作为恶性肿瘤的驱动因子，又可作为潜在的治疗介质——使其成为下一代免疫疗法研究的前沿焦点。作为治疗靶点，相关策略包括阻断巨噬细胞募集（如使用CSF-1/CSF-1R抑制剂）、选择性清除特定TAM亚群（如通过叶酸受体β途径），或将免疫抑制性的M2型巨噬细胞重编程为抗肿瘤的M1表型。另一方面，巨噬细胞亦可作为治疗工具——可通过工程化改造增强抗肿瘤免疫（如嵌合抗原受体巨噬细胞CAR-Ms的开发），或作为靶向药物递送载体将药物精准运输至肿瘤微环境。其中一项创新性策略是巨噬细胞-药物偶联物（MDCs），该技术利用铁结合蛋白转运（TRAIN）机制实现治疗药物的精准细胞内递送，从而在增强药效的同时降低全身毒性。本综述整合了当前对TAM生物学的认知，重点阐述了新兴治疗策略，并强调了基于巨噬细胞的干预手段在卵巢癌治疗中的潜力。通过将靶向巨噬细胞的策略与先进免疫治疗平台相结合，有望确立新的治疗范式，从而显著改善卵巢癌及其他实体瘤患者的临床结局。我们的研究强调，巨噬细胞应成为癌症治疗领域的重要研究方向。
Macrophages—Target and Tool in Tumor Treatment: Insights from Ovarian Cancer
肿瘤(癌症)患者之家