Phagocytosis of Glioma Cells Enhances the Immunosuppressive Phenotype of Bone Marrow-Derived Macrophages.
Cancer Res
; 83(5): 771-785, 2023 03 02.
Article
in En
| MEDLINE
| ID: mdl-36622331
ABSTRACT
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Phagocytosis
/
Glioblastoma
/
Glioma
/
Macrophages
Limits:
Humans
Language:
En
Journal:
Cancer Res
Year:
2023
Type:
Article
Affiliation country:
China