Background

Osteosarcoma (OS) is the most common primary malignant bone tumor. Compared with previous treatment modalities, such as amputation, more recent comprehensive treatment modalities based on neoadjuvant chemotherapy combined with limb salvage surgery have improved the survival rates of patients. Osteosarcoma treatment has, however, not further improved in recent years. Therefore, attention has shifted to the tumor microenvironment (TME) in which osteosarcoma cells are embedded. Therapeutic targets in the TME may be key to improving osteosarcoma treatment. Tumor-associated macrophages (TAMs) are the most common immune cells within the TME. TAMs in osteosarcoma may account for over 50% of the immune cells, and may play important roles in tumorigenesis, angiogenesis, immunosuppression, drug resistance and metastasis. Knowledge on the role of TAMs in the development, progression and treatment of osteosarcoma is gradually improving, although different or even opposing opinions still remain.

Conclusions

TAMs may participate in the malignant progression of osteosarcoma through self-polarization, the promotion of blood vessel and lymphatic vessel formation, immunosuppression, and drug resistance. Besides, various immune checkpoint proteins expressed on the surface of TAMs, such as PD-1 and CD47, provide the possibility of the application of immune checkpoint inhibitors. Several clinical trials have been carried out and/or are in progress. Mifamotide and the immune checkpoint inhibitor Camrelizumab were both found to be effective in prolonging progression-free survival. Thus, TAMs may serve as attractive therapeutic targets. Targeting TAMs as a complementary therapy is expected to improve the prognosis of osteosarcoma. Further efforts may be made to identify potential beneficiaries of TAM-targeted therapies.

中文翻译：

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肿瘤相关巨噬细胞在骨肉瘤进展中的作用——治疗意义

背景

骨肉瘤（OS）是最常见的原发性恶性骨肿瘤。与以往的截肢等治疗方式相比，新辅助化疗联合保肢手术的综合治疗方式提高了患者的生存率。然而，近年来骨肉瘤的治疗并没有进一步改善。因此，注意力已经转移到骨肉瘤细胞嵌入的肿瘤微环境（TME）上。TME 中的治疗目标可能是改善骨肉瘤治疗的关键。肿瘤相关巨噬细胞 (TAM) 是 TME 中最常见的免疫细胞。骨肉瘤中的 TAMs 可能占免疫细胞的 50% 以上，并且可能在肿瘤发生、血管生成、免疫抑制、耐药和转移中发挥重要作用。

结论

TAMs可能通过自极化、促进血管和淋巴管形成、免疫抑制和耐药等参与骨肉瘤的恶性进展。此外，TAMs表面表达的多种免疫检查点蛋白，如PD-1和CD47，为免疫检查点抑制剂的应用提供了可能。几项临床试验已经进行和/或正在进行中。Mifamotide 和免疫检查点抑制剂 Camrelizumab 均被发现可有效延长无进展生存期。因此，TAMs 可以作为有吸引力的治疗靶点。靶向 TAM 作为补充疗法有望改善骨肉瘤的预后。可能会进一步努力确定 TAM 靶向治疗的潜在受益者。