Table 1. TAM phenotype and signaling pathway in various solid tumors and blood cancers.
| Cancer type (solid and blood malignancies) | Macrophage phenotype | Signaling pathway | References |
|---|---|---|---|
| Breast cancer | IL-4/IL-13 stimulated macrophages; M2a derived CCL18 and VEGF promote metastasis in breast cancer; M1-like macrophages helps in the infiltration of CTLs, CD8 T cells and undergoes the inflammatory cytokine cascade to eliminate the tumor; CD68+ macrophages; COX2+; CD163+ | Signaling pathway involved—ROCK signaling; COX2+ TAMs activate PI3K-AKT pathway in cancer cells | (4-7) |
| Prostate cancer | CD206; TNF-α and IL-1β | TAMs promote prostate cancer progression through the activation of the CCL2–CCR2 axis, followed by the activation of the CCL17/CCL22–CCR4 axis; prostate cancer derived CCN3 mediates polarization to protumoral M2-like macrophages; VEGF mediated angiogenesis | (8-10) |
| Lung cancer (NSCLC) | CD204+ M2 and pan-CD68+ TAMs found in both stromal and intratumoral component | M2-like macrophages promote migration and angiogenesis in NSCLC via associated factors like MMP and VEGF | (11,12) |
| Ovarian cancer | M2-like macrophages with phenotype IL-10, CD163, CD204; CD206(MR) overexpressing CCL18 and CCL22 | M2-like macrophages enhance cancer cell proliferation via MMP9/HB-EGF axis. This EGF leads to αMβ2 integrin upregulation which further increases EGFR, ICAM-1 expression and then activates the VEGF/VEGFR pathway promoting angiogenesis and thus metastasis; the main TF involved is IRF4 | (13-19) |
| Glioblastoma | M2 marker arginase 1 was upregulated (10-fold) and also IL-1β upregulated (5-fold) | ERK1/2 signaling regulates macrophage recruitment in glioblastoma | (20-22) |
| Blood cancer | CD163+ M2 TAMs (mouse) and CD163+CD206+ M2 TAMs in multiple myeloma and classical Hodgkin Lymphoma; CLL: Markers expressed were: CD11b, CD163, CD206, HLA-DR, HGF, IDO—all resembling M2 phenotype. Burger et al. first found nurse like cells helping CLL microenvironment to be tumor supporting and later Tsukada et al. demonstrated that these were component of the TME similar to the TAMs in solid tumors; AML: splenic leukemia-associated macrophages turned out to have M2 characteristics while bone marrow leukemia-associated macrophages turned out M1 characterized | ALL: proliferation of T-ALL cell lines showed significant increase after being co-cultured with M2 macrophage subset due to secretion of TNFα, growth related oncogeneα, C5a, IL-6, CCL1 | (23-31) |
| Pancreatic cancer (PC) | REDD–; CD163+ M2-polarized macrophages were significantly more abundant in primary PDA samples | M2 TAMs found in the TME is associated to YAP1 signaling which correlates with tumorigenesis in many cancer types. YAP1/HIF-α pathway has been recently found responsible for promoting cancer stem cells in PC. REDD1 deficient TAMs outplay normal cells and form more vascular junctions favoring angiogenesis; notch signaling plays a role in macrophage polarization within the PDA (pancreatic ductal adenocarcinoma) microenvironment; pancreatic cancer-educated macrophages induced the upregulation of CD59 in pancreatic cancer cells via the IL-6R/STAT3 pathway; YAP1/HIF-α pathway | (32-35) |
TF, transcription factor.