Tumor-associated macrophages (tumor microenvironment) are macrophages that persist within tumors and act as central regulators of the tumor microenvironment, often adopting an immunosuppressive, pro-tumor state. A key mechanism highlighted here is tumor-derived IFN-driven niche reprogramming, where these cells persist in resistant lesions and acquire enhanced suppressive features, including SPP1/osteopontin expression. They are also shaped by lipid metabolic reprogramming, which promotes an immunosuppressive TAM phenotype, while broader metabolic state changes are being explored as a therapeutic lever to shift anti-tumor immunity. In glioblastoma, TAMs can comprise a substantial fraction of the tumor microenvironment and are associated with poor prognosis, and in lung cancer spatial profiling identified a ring of lipid-associated TAMs lining the tumor edge. Recent studies also report that TAMs are typically M2-polarized but can be reprogrammed toward an M1-like state, supporting macrophage-directed immunotherapy strategies.
Tumor microenvironment and resistance
- Tumor cell-derived IFN spatially reprogrammed osteopontin-enriched macrophage niches, and these TAMs persisted in resistant lesions with enhanced immunosuppressive features. (PMID:41734034)
- The resistant macrophage niche was characterized by SPP1 expression, linking TAM state to PARP inhibitor resistance. (PMID:41734034)
- TAMs were described as central regulators of the tumor microenvironment, emphasizing their role in shaping local immune suppression. (PMID:41961489)
- Lipid metabolic reprogramming in the tumor microenvironment promoted an immunosuppressive macrophage population. (PMID:41946907)
Glioblastoma
- In glioblastoma, TAMs were reported to make up a substantial portion of the tumor microenvironment and were associated with poor prognosis. (PMID:41582518)
- In vitro generated macrophages were shown to reflect the immunosuppressive phenotype of in vivo glioblastoma-associated macrophages. (PMID:41582518)
- A murine-based model was used to generate glioblastoma TAM-like macrophages from bone-marrow-derived glioma-educated macrophages. (PMID:41582518)
Lung cancer and spatial niches
- Multiomics immune profiling with SEPARATE-Seq identified a ring of lipid-associated TAMs lining the tumor edge in an orthotopic lung cancer model. (PMID:42026061)
- Spatial transcriptomics was used to define this edge niche of lipid-associated TAMs. (PMID:42026061)
- Biomimetic proteolipid vesicles delivering small activating RNA were used to activate macrophage immunotherapy for lung cancer, indicating a strategy to reprogram TAM function. (PMID:41992232)
Macrophage reprogramming and metabolism
- TAM metabolism was proposed as a therapeutic target for reprogramming anti-tumor immunity. (PMID:41961489)
- Macrophages in the tumor microenvironment were described as typically polarizing toward an M2 phenotype, but this study reprogrammed them toward an M1 phenotype. (PMID:41992232)
- Lipid metabolism reprogramming was linked to shaping the immune landscape in the tumor microenvironment. (PMID:41946907)