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The immune regulatory function of B7-H3 in malignancy: spotlight on the IFN-STAT1 axis and regulation of tumor-associated macrophages

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A Correction to this article was published on 22 February 2024

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Abstract

B7-H3 is a member of the B7 superfamily and a putative inhibitory immune checkpoint molecule. Several early-phase clinical trials have reported promising anti-tumor activity and safety of anti-cancer drugs targeting B7-H3, suggesting that it may be a promising target for a potential next-generation immune checkpoint inhibitor. Despite ongoing clinical studies, most B7-H3-targeted drugs being currently investigated rely on direct cytotoxicity as their mechanisms of action rather than modulating its function as an immune checkpoint, at least in part due to its incompletely understood immune regulatory function. Recent studies have begun to elucidate the role of B7-H3 in regulating the tumor microenvironment (TME). Emerging evidence suggests that B7-H3 may regulate the interferon-STAT1 axis in the TME and promote immune suppression. Similarly, increasing evidence shows B7-H3 may be implicated in promoting M1 to M2 polarization of tumor-associated macrophages (TAMs). There is also accumulating evidence suggesting that B7-H3 may play a role in the heterotypic fusion of cancer stem cells and macrophages, thereby promoting tumor invasion and metastasis. Here, we review the recent advances in the understanding of B7-H3 cancer immunobiology with a focus on highlighting its potential role in the interferon priming of TAMs and the heterotypic fusion of TAMs with cancer stem cells and suggest future direction in elucidating its immune checkpoint function.

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This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT, and Future (2022R1A2C1003860 to Jong Dae Ji).

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Authors and Affiliations

  1. Department of Hematology/Oncology, Moffitt Cancer Center/University of South Florida, Tampa, FL, USA

    Robin Park, James Yu & Moazzam Shahzad

  2. Department of Internal Medicine, Korea University, Seoul, South Korea

    Sunggon Lee

  3. Department of Rheumatology, College of Medicine, Korea University, Seoul, South Korea

    Jong Dae Ji

Authors
  1. Robin Park
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  2. James Yu
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  3. Moazzam Shahzad
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  4. Sunggon Lee
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  5. Jong Dae Ji
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Contributions

Conceptualization: R.P. and J.J.; validation: R.P., J.Y., M.S., S.L., and J.J.; writing—original draft preparation: R.P. and J.J.; writing—review and editing: R.P., J.Y., M.S., S.L., and J.J.; visualization: R.P.; supervision: J.J.; project administration: R.P. and J.J. All authors have read and agreed to the published version of the manuscript.

Corresponding author

Correspondence to Jong Dae Ji.

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The original online version of this article was revised: A spelling error was identified in an author’s name, which has been corrected. Namely, Dr. Moazzam Shazad’s name has been corrected to “Shahzad”. The affiliation 1 were corrected from “Department of Hematology/Oncology, Moffitt Cancer Center, Tampa, FL, USA” to “Department of Hematology/Oncology, Moffitt Cancer Center/University of South Florida, Tampa, FL, USA.

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Park, R., Yu, J., Shahzad, M. et al. The immune regulatory function of B7-H3 in malignancy: spotlight on the IFN-STAT1 axis and regulation of tumor-associated macrophages. Immunol Res (2024). https://doi.org/10.1007/s12026-024-09458-9

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  • DOI: https://doi.org/10.1007/s12026-024-09458-9

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