Review
Copyright ©The Author(s) 2023.
World J Gastrointest Oncol. Apr 15, 2023; 15(4): 596-616
Published online Apr 15, 2023. doi: 10.4251/wjgo.v15.i4.596
Table 1 Tumor-associated macrophages can promote the development of tumors
Diseases
Factors
Functions
Mechanism
Ref.
ECGDF-15 derived from TAMsPromoting progression of ESCCActivating TGF-β type II receptor[44]
GCTAMsPromoting peritoneal dissemination of GCSecreting IL-6[53]
TAMsPromoting progression in GCPolarizing to the M2 phenotype[54]
TAMsSupporting peritoneal metastasisProducing EGF and VEGF[55]
TNF-alpha and IL-6 secreted by TAMsPromoting proliferation of GC cellsActivating the NF-κB and STAT3 signaling pathway to regulate PD-L1 expression[56]
TGFβ2 secreted by TAMsPromoting the invasion of GC cellsRegulating Kindlin-2 through NF-κB[57]
CCL5 secreted by TAMsPromoting the proliferation, invasion and metastasis of GC cellsStat3 signaling pathway[58]
TAMsInfluencing omental milky spots and lymph nodes micrometastasisCOX-2/PGE-2/TGF-β/VEGF signal pathways[59]
TAMsPromoting epigenetic silencing of tumor suppressor gelsolin, and silence GSNUpregulation of DNMT1 by CCL5/CCR5/STAT3 signaling[60]
TAMsInducing invasion and poor prognosis in GCPromoting MMP9 expression[63]
MMP-9 secreted by TAMsSuppressing distant metastasis in GCPI3K/AKT/Snail dependent pathway[64]
Exosomal miR-487a derived from TAMsPromoting the proliferation and tumorigenesis in GC-[65]
M2 macrophage-derived exosomesRemodeling the cytoskeleton-supporting migration in recipient GC cellsMediating an intercellular transfer of ApoE-activating PI3K-Akt signaling pathway[66]
CRCTAMsPotentiating the angiogenic capacity of the TMEOxidative stress-dependent manner[91]
Metabolic reprogramming in TAMsBuilding a bridge between metabolic dysfunction and the onset and progression of CRCInflammatory pathways[92]
M2 macrophage-derived exosomesPromoting CRC cells’ migration and invasionMiR-21-5p and miR-155-5p[93]
Exosomal miR-183-5p Shuttled by M2 TAMsPromoting the development of colon cancerTHEM4 mediated PI3K/AKT and NF-κB pathways[94]
MMP1 derived from TAMsFacilitating colon cancer cell proliferationAccelerating cell cycle transition from G0/G1 to S and G2/M phase[95]
M2 TAMsInducing colon cancer cell invasionMMP-9[96]
Cathelicidin secreted by TAMsPromoting the growth of CRCRecruiting inflammatory cells[97]
PCIntraperitoneal TAMsPromoting peritoneal dissemination and chemoresistanceInducing EMT[123]
M2 TAMsPromoting EMTTLR4/IL-10 signaling[124]
TAMsPromoting progression and the Warburg effectCCL18/NF-Kb/VCAM-1 pathway[125]
CCL20 secreted by M2 TAMsPromoting the migration, epithelial-mesenchymal transition, and invasion of pancreatic cancer cells-[126]
TAMsOrchestrating functions PDA-infiltrating T cellsOdulating PDA-infiltrating T cells epigenetic profile towards a pro-tumoral phenotype[42]
LCTAMsPromoting LCSLC self-renewal capability and carcinogenicityM2 polarization[151]
TAMsPromoting EMT of Hep3B hepatoma cellsTLR4[153]
IL-6 secreted by TAMsPromoting expansion of these CSCs and tumorigenesisSTAT3 signaling[154]
Table 2 Tumor-associated macrophages act as potential therapeutic targets for tumors
Diseases
Factors
Types
Targets
Functions
Mechanism
Ref.
ECMiR-498MiRNAInhibiting autophagy and M2-like polarization of TAMs in esophageal cancer-Inhibiting MDM2-mediated ATF3 degradation[45]
MiR-155MiRNARegulating TAMs FGF2 expressionSuppressing EC cell proliferation, migration, invasion and inhibiting vasculature formation-[46]
EC-Derived Extracellular Vesicle miR-21-5pMiRNADisorganizing macrophages polarizationContributing to EMT of ESCC cells via TGF-β/Smad2 signalingPTEN/AKT/STAT6 pathway[47]
PTENProteinInducing M2 TAMs polarizationEnhancing the malignant behavior of TECs, promoting ESCC angiogenesisActivating the PI3K/AKT signaling pathway[48]
NCAM- and FGF-2-mediated FGFR1 signalingSignalingRegulating the survival and migration of TAMs and cancer cells-NCAM knockdown via a suppression of PI3K-Akt and FGFR1 signaling, and rhFGF-2 -through FGFR1 signaling[49]
HR-HPV; HPV16 infectionVirusPromoting M2 macrophages phenotypePromoting the invasion and metastasis of esophageal squamous cell carcinoma-[50]
GCSTINGGenePromoting TAMs polarizing into pro-inflammatory subtypeInducing apoptosis of GC cellsIL6R-JAK-L24pathway[67]
LINC00665LncRNAActivating Wnt1 and mediating TAMs M2 polarization-Interacting with BTB domain and BACH1[68]
CALM2ProteinPolarizing TAMsFacilitating angiogenesis and metastasis of GCSTAT3/HIF-1A/VEGF-A[69]
MENKProteinSkewing macrophages toward M2 phenotype from M1 phenotypeInducing cells apoptosisOGFr/PI3K/AKT/Mtor signaling pathway[70]
ELK4Transcription factorPromoting M2 polarizationPromoting the development of GCReducing the PJA2-dependent inhibition of KSR1 by transcriptional activation of KDM5A[71]
IL-6CytokinePolarizing the MφsPromoting tumor invasionIL-6/STAT3/IRF4 signaling pathway[72]
GC-MSCsCellPromoting M2 polarizationPromoting metastasis and EMT in GCSecreting IL-6 and IL-8[73]
Vasoactive intestinal peptideProteinRepressing activation of TAMs-Regulating TNFα, IL-6, IL-12 and Inos[74]
Lipid droplet-dependent fatty acidFatty acidControlling the immune suppressive phenotype of TAMs--[75]
MiR-151-3p derived from GC exosomesExosomeInducing M2-phenotype polarizationPromoting tumor growth-[76]
IL-33-mediated mast cellCellMobilizing macrophagesPromoting GC-[77]
CRCPKN2ProteinInhibiting M2 phenotype polarization-DUSP6-Erk1/2 pathway[98]
AQP9ProteinStimulating M2-like polarizationPromoting colon cancer progressionTransporting lactate[99]
PKCαTumor suppressorPromoting M1 macrophages polarization-MKK3/6-P38 signaling pathway[100]
MK2ProteinPromoting polarization of protumorigenic TAMs--[101]
MiR-195-5p/NOTCH2-mediated EMT-Affecting M2-like TAMs polarization-Modulating IL-4 secretion[102]
CRC cell-derived exosomal miR-934ExosomeInducing M2 macrophages polarization-Downregulating PTEN expression and activate the PI3K/AKT signaling pathway[103]
Stimulator of STING pathwaySignaling pathwayActivating reprogramed TAMs toward the M1 phenotype--[104]
Colon cancer cellCellPromoting M2 polarization of TAMs-Secreting EGF; EGFR/PI3K/AKT/Mtor pathway[105]
CXCL10 and CXCL11ChemokineInducing the infiltration of TAMsLeading to the poor prognosis of CRC-[106]
β-1, 6-glucanOrganic compoundReseting TAMs from M2-like to M1-like phenotypeInhibiting the viability of colon cancer cellsIncreasing the phosphorylation of Akt/NF-κB and MAPK[107]
H. pylori infectionBecteriaReducing the infiltration of M2-like TAMs-Downregulating TNF-α, IL-1β, IL-6 and IL-23[108]
PCAutophagy-dependent ferroptosis-Driving TAMs polarization-Releasing and uptaking of oncogenic KRAS protein[127]
RIP1KinaseReprogramming TAMs-STAT1-dependent manner[40]
Deletion of CAF-HIF2ProteinDecreasing the intratumoral recruitment of immunosuppressive M2 macrophages--[128]
ADH-503Small-molecule agonistLeading to the repolarization of TAMs-Partial activation of CD11b[129]
NLRP3InflammasomeRegulating TAMs polarizationEnhancing lung metastasis of PDAC-[130]
IL-27CytokineTargeting M2 TAMsDampening the proliferation, migration and metastasis of PC cells-[131]
IFN-γChemokinesPreventing trafficking of TAMsImproving the efficacy of PD1 blockade therapy in PCBlocking the CXCL8-CXCR2 axis[132]
PC-derived exosomal FGD5-AS1ExosomeStimulating M2 macrophages polarizationPromoting proliferation and migration of PC cellActivating STAT3/NF-κB pathway[133]
PDAC-derived Sev-EZRExosomeModulating TAMs polarizationPromoting PDAC metastasis-[134]
CUX1Transcription factorMediating M1 polarizationInhibiting angiogenesis and tumor progressionDownregulating several NF-κB -regulated chemokines[135]
Tryptophan-derived microbial metaboliteMetaboliteActivating the aryl hydrocarbon receptor in TAMsSuppressing anti-tumor immunity-[136]
Nrf2Transcription factorStimulating M2 macrophages polarizationPromoting EMTActivating cancer cell-derived lactate[137]
Lactic acidOrganic compoundRedistributing M2TAMs subsetsUpregulating PDL1 to assist tumor immune escapeHIF1α signaling pathway[138]
Activation of DRD4 by DAProteinSuppressing the tumor-promoting inflammation of TAMs-Decreasing Camp; inhibit the activation of PKA/p38 signal pathway[139]
PDA cellsCellReprogramming M1-like macrophages-GARP-dependent and DNA methylation-mediated mechanism[140]
LCNdrg2GeneInfluencing TAMs polarization-NF-κB pathway[155]
TREM1knockdownGeneShifting M2 macrophages towards a M1 phenotype-Inhibiting PI3K/AKT/Mtor activation[156]
MiR-99bMiRNAPromoting M1 while suppressing M2 macrophages polarization-Targeting κB -Ras2 and/or mTOR[157]
MAGLKinasePromoting the transcription and secretion of inflammatory factors in TAMs--[158]
--Blocking triggering receptor expressed on myeloid cells-1-positive TAMsReversing immunosuppression and anti-PD-L1 resistance in LC-[159]
RegorafenibMultikinase inhibitorsReversing M2 polarization-Suppressing p38 kinase phosphorylation and downregulating Creb1/Klf4 activity in BMDMs[160]
ZIP9ProteinPromoting M2 macrophages polarization-Enhancing phosphorylated STAT6[161]
Phosphoinositide-related signaling pathwaySignaling pathwayReprogramming TAMs-Enhancing activation of the PI3K/Akt pathway[162]
Inhibite VEGF signaling pathwaySignaling pathwayAttenuating TAMs activity in liver cancer--[163]
SALL4-mediated upregulation of exosomal miR-146a-5pExosomeLeading to M2-polarized TAMs-Activating NF-κB signaling and inducing pro-inflammatory factors[43]
Activated HSCsCellConverting macrophages to TAMs--[164]