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The role of tumor-associated macrophages in osteosarcoma progression – therapeutic implications

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Abstract

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.

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Acknowledgements

This work was supported by the Beijing Science and Technology Project (No. Z161100000116100) and the National Natural Science Foundation of China (No.81572633 and No.82072970).

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  1. Musculoskeletal Tumor Center, Peking University People’s Hospital, Beijing, China

    Qingshan Huang, Xin Liang, Tingting Ren, Yi Huang, Hongliang Zhang, Yiyang Yu, Chenglong Chen, Wei Wang, Jianfang Niu, Jingbing Lou & Wei Guo

  2. Beijing Key Laboratory of Musculoskeletal Tumor, Beijing, China

    Qingshan Huang, Xin Liang, Tingting Ren, Yi Huang, Hongliang Zhang, Yiyang Yu, Chenglong Chen, Wei Wang, Jianfang Niu, Jingbing Lou & Wei Guo

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Wei Guo perceived the article, Qingshan Huang, Xin Liang, Tingting Ren, Yi Huang, Hongliang Zhang, Yuyang Yi, Chenlong Chen, Wei Wang, Jianfang Niu and Jingbing Lou performed the literature search and data analysis, and Wei Guo, Qingshan Huang and Xin Liang drafted and critically revised the work.

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Huang, Q., Liang, X., Ren, T. et al. The role of tumor-associated macrophages in osteosarcoma progression – therapeutic implications. Cell Oncol. 44, 525–539 (2021). https://doi.org/10.1007/s13402-021-00598-w

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