Phagocytosis of Glioma Cells Enhances the Immunosuppressive Phenotype of Bone Marrow-Derived Macrophages

Cancer Res. 2023 Mar 2;83(5):771-785. doi: 10.1158/0008-5472.CAN-22-1570.


Tumor-associated macrophages (TAM) play a crucial role in immunosuppression. However, how TAMs are transformed into immunosuppressive phenotypes and influence the tumor microenvironment (TME) is not fully understood. Here, we utilized single-cell RNA sequencing and whole-exome sequencing data of glioblastoma (GBM) tissues and identified a subset of TAMs dually expressing macrophage and tumor signatures, which were termed double-positive TAMs. Double-positive TAMs tended to be bone marrow-derived macrophages (BMDM) and were characterized by immunosuppressive phenotypes. Phagocytosis of glioma cells by BMDMs in vitro generated double-positive TAMs with similar immunosuppressive phenotypes to double-positive TAMs in the GBM TME of patients. The double-positive TAMs were transformed into M2-like macrophages and drove immunosuppression by expressing immune-checkpoint proteins CD276, PD-L1, and PD-L2 and suppressing the proliferation of activated T cells. Together, glioma cell phagocytosis by BMDMs in the TME leads to the formation of double-positive TAMs with enhanced immunosuppressive phenotypes, shedding light on the processes driving TAM-mediated immunosuppression in GBM.

Significance: Bone marrow-derived macrophages phagocytose glioblastoma cells to form double-positive cells, dually expressing macrophage and tumor signatures that are transformed into M2-like macrophages and drive immunosuppression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • B7 Antigens
  • Glioblastoma* / genetics
  • Glioblastoma* / immunology
  • Glioblastoma* / pathology
  • Glioma* / metabolism
  • Glioma* / pathology
  • Humans
  • Macrophages* / immunology
  • Macrophages* / metabolism
  • Phagocytosis*
  • Phenotype
  • Tumor Microenvironment / immunology


  • B7 Antigens
  • CD276 protein, human