Role of tumor-associated macrophages in common digestive system malignant tumors

Table 1 Tumor-associated macrophages can promote the development of tumors

Diseases	Factors	Functions	Mechanism	Ref.
EC	GDF-15 derived from TAMs	Promoting progression of ESCC	Activating TGF-β type II receptor	[44]
GC	TAMs	Promoting peritoneal dissemination of GC	Secreting IL-6	[53]
	TAMs	Promoting progression in GC	Polarizing to the M2 phenotype	[54]
	TAMs	Supporting peritoneal metastasis	Producing EGF and VEGF	[55]
	TNF-alpha and IL-6 secreted by TAMs	Promoting proliferation of GC cells	Activating the NF-κB and STAT3 signaling pathway to regulate PD-L1 expression	[56]
	TGFβ2 secreted by TAMs	Promoting the invasion of GC cells	Regulating Kindlin-2 through NF-κB	[57]
	CCL5 secreted by TAMs	Promoting the proliferation, invasion and metastasis of GC cells	Stat3 signaling pathway	[58]
	TAMs	Influencing omental milky spots and lymph nodes micrometastasis	COX-2/PGE-2/TGF-β/VEGF signal pathways	[59]
	TAMs	Promoting epigenetic silencing of tumor suppressor gelsolin, and silence GSN	Upregulation of DNMT1 by CCL5/CCR5/STAT3 signaling	[60]
	TAMs	Inducing invasion and poor prognosis in GC	Promoting MMP9 expression	[63]
	MMP-9 secreted by TAMs	Suppressing distant metastasis in GC	PI3K/AKT/Snail dependent pathway	[64]
	Exosomal miR-487a derived from TAMs	Promoting the proliferation and tumorigenesis in GC	-	[65]
	M2 macrophage-derived exosomes	Remodeling the cytoskeleton-supporting migration in recipient GC cells	Mediating an intercellular transfer of ApoE-activating PI3K-Akt signaling pathway	[66]
CRC	TAMs	Potentiating the angiogenic capacity of the TME	Oxidative stress-dependent manner	[91]
	Metabolic reprogramming in TAMs	Building a bridge between metabolic dysfunction and the onset and progression of CRC	Inflammatory pathways	[92]
	M2 macrophage-derived exosomes	Promoting CRC cells’ migration and invasion	MiR-21-5p and miR-155-5p	[93]
	Exosomal miR-183-5p Shuttled by M2 TAMs	Promoting the development of colon cancer	THEM4 mediated PI3K/AKT and NF-κB pathways	[94]
	MMP1 derived from TAMs	Facilitating colon cancer cell proliferation	Accelerating cell cycle transition from G0/G1 to S and G2/M phase	[95]
	M2 TAMs	Inducing colon cancer cell invasion	MMP-9	[96]
	Cathelicidin secreted by TAMs	Promoting the growth of CRC	Recruiting inflammatory cells	[97]
PC	Intraperitoneal TAMs	Promoting peritoneal dissemination and chemoresistance	Inducing EMT	[123]
	M2 TAMs	Promoting EMT	TLR4/IL-10 signaling	[124]
	TAMs	Promoting progression and the Warburg effect	CCL18/NF-Kb/VCAM-1 pathway	[125]
	CCL20 secreted by M2 TAMs	Promoting the migration, epithelial-mesenchymal transition, and invasion of pancreatic cancer cells	-	[126]
	TAMs	Orchestrating functions PDA-infiltrating T cells	Odulating PDA-infiltrating T cells epigenetic profile towards a pro-tumoral phenotype	[42]
LC	TAMs	Promoting LCSLC self-renewal capability and carcinogenicity	M2 polarization	[151]
	TAMs	Promoting EMT of Hep3B hepatoma cells	TLR4	[153]
	IL-6 secreted by TAMs	Promoting expansion of these CSCs and tumorigenesis	STAT3 signaling	[154]

Tumor-associated macrophages (TAMs) contribute to the development of esophageal cancer, gastric cancer, colorectal cancer, pancreatic cancer and liver cancer. The effective factors are TAMs and their derivants or secretions. The function indicates that how these factors exert influence on tumor progression, concerning proliferation, invasion, metastasis, migration and so on. In addition, the mechanism indicates the corresponding signaling pathways or regulatory intermediates, through which TAMs and their derivants promote or suppress development of the cancers. The last column indicates the corresponding reference of the entry. EC: Esophageal cancer; GC: Gastric cancer; CRC: Colorectal cancer; PC: Pancreatic cancer; LC: Liver cancer; GDF-15: Growth/differentiation factor-15; TAM: Tumor-associated macrophages; ESCC: Esophageal squamous cell carcinoma; TGF-β: Transforming growth factor-β; IL: Interleukin; EGF: Epidermal growth factor; VEGF: Vascular endothelial growth factor; TNF-α: Tumor necrosis factor-α; NF-kB: Nuclear factor kB; STAT3: Signal transducers and activator of transcription 3; PD-L1: Programmed Cell Death Ligand 1; PGE-2: Prostaglandin E2; PI3K: Phosphoinositide 3-kinase; MMP9: Matrix metalloproteinases 9; CCL5: CC ligand 5; TLR4: Toll like receptor 4; LCSLC: Liver cancer stem-like cell; CSC: Cancer stem cell.