Table 1.
Studies on the role of macrophages in osteosarcoma.
| Type of Study | Markers and TAM Phenotype | Findings | References |
|---|---|---|---|
| Human samples, GEP and IHC analysis | CD14/HLA-DRα (M1); CD14/CD163 (M2) |
Higher CD14+ TAMs levels correlated with better OS and metastasis suppression with no clinical relevance between M1/M2 phenotype | [15] |
| Human samples, IHC analysis | CD163 (M2); | Better overall survival and prolonged metastasis progression-free survival. | [16] |
| Human samples, IHC analysis | CD68/iNOS/COX-2 (M1); CD163 (M2); | Higher CD68+/COX-2 levels in lung metastasis, unchanged CD163+ compared to paients with primary tumours while iNOS+ was relatively higher. | [17] |
| Pre-clinical study (THP-1 human cell line) | CD206/CD163 (M2); | BALB/c mice subcutaneously injected with THP-1 cell line promoted migration/invasion of OS cells through MO/M2 TAMs, showing higher levels of ZEB-1 and SNAIL toward an EMT phenotype. | [17] |
| Human samples, FACS analysis | CD14/CD163 (M2); | Higher CD163+ TAMs levels in primary tumour than PB and TILs correlated with lower levels of TIM-3+/PD-1+ T cells. | [18] |
| Human samples, IHC analysis | CD68/iNOS (M1); | Higher CD68/iNOS+ level in non metastatic patients’ group, with better OS | [19] |
| Pre-clinical study (U2OS human cell line) | F4/F80/CD163 (M2) | NOD/SCID mice orthotopically injected with OS cells show the recruitment of CD163+ M2 TAMs subtype and a higher tumour growth. | [20] |
| Pre-clinical study (K7M2 mouse cell line) | CD163/CD209/MRC1/CCR2/F4/80 (M2); | BALB/c mice orthotopically co-injected with OS with or w/out RAW264.7 cells treated with ATRA show reduced M2-polarization through suppressing colony/sarcosphere formation and tumour growth. | [21] |
| Human samples, single cell RNA seq analysis | CD163/MRC1/MS4A4/MAF (M2); FABP4+ (M3); | M1-, M2- and M3 TAMs are the 80% of the major macrophages cell subtypes in the myeloid compartment of OS lesions, while the FABP4+ M3 levels are directly correlated with the metastatic spread through the lung. | [22] |
| Human samples, CIBERSORT algorithm | Defined by CIBERSORT | M0 and M2 are the most relevant cell subtypes in patients’ metastatic samples. | [23] |
| Human samples, CIBERSORT and TIMER analysis | Defined by CIBERSORT | Lower levels of M2 TAMs directly associated with patients’ poor survival. | [24] |
| Human samples, GEP and TIMER analysis | Defined by CIBERSORT | Higher M1/M2 TAMs levels in the infiltrating microenvironment showed an improved overall survival of patients; better OS | [25] |
Footnotes. TAMs: Tumor associated macrophages; PB: peripheral blood; TILs: tumor infiltrating T cells; ATRA: all-trans retinoic acid; EMT: epithelial to mesenchymal transition; GEP: gene expression profile; IHC: immunohistochemistry; FACS: fluorescent-activated cell sorting.