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Phenotypic plasticity of myeloid cells in glioblastoma development, progression, and therapeutics

Oncogene volume 40, pages 6059–6070 (2021)Cite this article

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Abstract

Glioblastoma (GBM) is the most common and malignant type of intracranial tumors with poor prognosis. Accumulating evidence suggests that phenotypic alterations of infiltrating myeloid cells in the tumor microenvironment are important for GBM progression. Conventional tumor immunotherapy commonly targets T-cells, while innate immunity as a therapeutic target is an emerging field. Targeting infiltrating myeloid cells that induce immune suppression in the TME provides a novel direction to improve the prognosis of patients with GBM. The factors released by tumor cells recruit myeloid cells into tumor bed and reprogram infiltrating myeloid cells into immunostimulatory/immunosuppressive phenotypes. Reciprocally, infiltrating myeloid cells, especially microglia/macrophages, regulate GBM progression and affect therapeutic efficacy. Herein, we revisited biological characteristics and functions of infiltrating myeloid cells and discussed the recent advances in immunotherapies targeting infiltrating myeloid cells in GBM. With an evolving understanding of the complex interactions between infiltrating myeloid cells and tumor cells in the tumor microenvironment, we will expand novel immunotherapeutic regimens targeting infiltrating myeloid cells in GBM treatment and improve the outcomes of GBM patients.

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Fig. 1: Myeloid cells of glioma immune microenvironment.

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Acknowledgements

This work was supported by grants from National Natural Science Foundation of China (grant # 81822034 and grant # 81821002), National Key Research and Development Program of China (2017YFA0106800 and 2018YFA0109200), Sichuan Science-Technology International Cooperation Project (grant #2019YFH0144), Sichuan Science-Technology Key Research and Development Program (grant #2021YFS0015), Direct Scientific Research Grants from West China Second Hospital, Sichuan University (grant #KS021 and #K1907).

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  1. These authors contributed equally: Zengpanpan Ye, Xiaolin Ai.

Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Key Laboratory of Birth Defects and Related Diseases of Women and Children of Ministry of Education, West China Second Hospital and Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu, P. R. China

    Zengpanpan Ye, Xiaolin Ai, Ping Wang & Shengtao Zhou

  2. Division of Regenerative Medicine, Department of Medicine, University of California, San Diego, La Jolla, CA, USA

    Linjie Zhao

  3. Department of Neurosurgery, Sichuan Academy of Medical Sciences and Sichuan Provincial People’s Hospital; School of Medicine, University of Electronic Science and Technology of China, No.32 West Second Section First Ring Road, Chengdu, 610072, Sichuan, China

    Fan Fei

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STZ, PW, and ZPPY contributed to the conception of the review; STZ, ZPPY, FF, and XLA drafted the article; XLA, ZPPY, PW, and FF revised it critically; ZPPY and XLA drew the figure; all authors have provided approval of the paper final version.

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Ye, Z., Ai, X., Zhao, L. et al. Phenotypic plasticity of myeloid cells in glioblastoma development, progression, and therapeutics. Oncogene 40, 6059–6070 (2021). https://doi.org/10.1038/s41388-021-02010-1

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