Immunosuppressive myeloid cells, which are associated with resistance to anti-PD1 therapy in patients with glioblastoma, have high expression of KDM6B, an epigenetic enzyme. Deletion or inhibition of KDM6B reprograms the myeloid cells to an immunostimulatory phenotype and thereby overcomes resistance to anti-PD1 therapy in preclinical models of glioblastoma.
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14 September 2023
In the version of this article initially published, there was an error in the summary reference, which has been updated to cite Nat. Cancer https://doi.org/10.1038/s43018-023-00620-0 in the HTML and PDF versions of the article.
References
Preusser, M., Lim, M., Hafler, D. A., Reardon, D. A. & Sampson, J. H. Prospects of immune checkpoint modulators in the treatment of glioblastoma. Nat. Rev. Neurol. 11, 504–514 (2015). This review article discusses the role of immune checkpoint molecules in GBM and highlights pertinent challenges in the clinical development of immune checkpoint inhibitors for the treatment of GBM.
Goswami, S., Anandhan, S., Raychaudhuri, D. & Sharma, P. Myeloid cell-targeted therapies for solid tumours. Nat. Rev.Immunol. 23, 106–120 (2022). This review article provides an overview of the latest therapeutic strategies for modulatingmyeloid-cell-mediated anti-tumor immunity, including those that target epigenetic and metabolic pathways.
Cheng, S. et al. A pan-cancer single-cell transcriptional atlas of tumor infiltrating myeloid cells. Cell 184, 792–809.e723 (2021). This study identified distinct subsets of tumor-infiltrating myeloid cells in 210 patients with 15 cancer types.
Goswami, S. et al. Immune profiling of human tumors identifies CD73 as a combinatorial target in glioblastoma. Nat. Med. 26, 39–46 (2020). This study demonstrated the persistence of CD73hi macrophages in GBM after anti-PD1 therapy and also showed that therapeutic targeting of CD73 improves the response to anti-PD1 therapy in GBM.
Hong, S. et al. Identification of JmjC domain-containing UTX and JMJD3 as histone H3 lysine 27 demethylases. Proc. Natl Acad. Sci. USA 104, 18439–18444 (2007). This study identified KDM6B as an H3K27-specific demethylase and demonstrated the dynamic regulation of H3K27 methylation.
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This is a summary of: Goswami, S. et al. Myeloid-specific KDM6B inhibition sensitizes glioblastoma to PD1 blockade. Nat. Cancer https://doi.org/10.1038/s43018-023-00620-0 (2023).
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KDM6B-mediated reprogramming of myeloid cells regulates the response to immunotherapy. Nat Cancer 4, 1408–1409 (2023). https://doi.org/10.1038/s43018-023-00621-z
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DOI: https://doi.org/10.1038/s43018-023-00621-z
