TABLE 1.

Tumor-derived exosomal cargoes stimulate polarization of macrophages.

Exosomal cargo	Cancer type	Recipients	Role/Mechanism	Major outcomes	References
Cytoskeleton-Centric Proteins	Colorectal cancer	Macrophages	Activate cathepsin B/pro-inflammatory cytokine secretion	Promote inflammation	Chen et al. (2016)
Rab22a-NeoF1	Osteosarcoma	Macrophages	M2 polarization/STAT3/RhoA activation	Promote lung metastasis	Zhong et al. (2021)
MFG-E8	Prostate cancer	Macrophages	M2 polarization/Increase efferocytosis/Suppress proinflammatory response	Promote tumor progression	Soki et al. (2014)
CMTM6	OSCC	Macrophages	M2 polarization/ERK1/2 signaling	Facilitate proliferation, migration and invasion	Pang et al. (2021)
HMGB1	Esophageal squamous cell carcinoma	Macrophages	M2 polarization/Trigger clonal expansion of PD1+ TAM	Promote tumor development	Li et al. (2019)
gp130	Breast Cancer	Macrophages	Activate IL-6/STAT3 signaling	Establish a pro-tumorigenic cancer microenvironment	Ham et al. (2018)
Chondroitin Sulfate Proteoglycan 4/α-2-Macroglobulin/Lactadherin/EGFR/Integrins	Glioblastoma multiforme	Monocytes	Increase phagocytic capacity/Mediate monocytes differentiation into M2 macrophages	Resemble the tumor supportive phenotypes	de Vrij et al. (2015)
EIF2/mTOR/Ephrin B	Glioblastoma	Macrophage	M2 phenotype/Increase PD-L1 expression	Induce immunosuppressive microenvironment	Gabrusiewicz et al. (2018)
Serglycin	Myeloma	Target cell	Reprogram target cells/Increase the migration of macrophage	Promote proliferation and invasion	Purushothaman et al. (2017)
PRPS2	NSCLC	Macrophages	M2 polarization	Promote DDP resistance	Liu et al. (2021)
miR-203	Colorectal cancer	Monocytes	M2 polarization/Promote the expression of M2 markers	Distant metastasis	Takano et al. (2017)
miR-145	Colorectal cancer cells	Macrophage-like cells	M2-like phenotype/Downregulate histone deacetylase 11	Modulate M2-like macrophage polarization and tumor progression	Shinohara et al. (2017)
miR-29a-3p	Oral squamous cell carcinoma	Macrophages	M2 polarization/Activate SOCS1/STAT6 signals	Promote tumor growth	Cai et al. (2019)
miR-301a-3p	Hypoxic pancreatic cancer cells	Macrophages	M2 polarization/Activate the PTEN/PI3K signaling pathway	Facilitate the invasion, migration and EMT; increase metastatic ability	Wang et al. (2018)
miR-155/miR-125b-2	Panc-1 cells	M1 macrophages	Trigger M1 to M2 polarization/increase M2 markers/decrease M1 markers	Enhance antigen presentation/T-cell activation/tumor destruction	(Su et al., 2016)
		M2 macrophages	Repolarize from M2 to M1/high iNOs/Arg1 and IL-1β/Arg1 ratio	Tumor invasion and metastasis
miR-21/miR-155	Neuroblastoma	Unpolarized monocytes (prevalent M2)	Mixed polarization/exosomic mir-21/TLR8-NF-кB/exosomic mir-155/TERF1 signaling pathway	Development of drug resistance	Challagundla et al. (2015)
miR-146a-5p	Hepatocellular carcinoma	Macrophages	M2 polarization/activate NF-κB signaling/pro-inflammatory factors	Promote HCC progression	Yin et al. (2019)
miR-16	4T1 cells/Myeloma	Macrophages	Inhibit TAM infiltration and M2 polarization/IKKα suppression and I-κB accumulation	Suppress tumor growth	Jang et al. (2013); Khalife et al. (2019)
miR-125b-5p	Melanoma	Macrophages	TAM phenotype/target LIPA	Induce inflammation and angiogenesis; cell recruitment and survival	Gerloff et al. (2020)
miR-222-3p	Epithelial ovarian cancer	Macrophage	M2 polarization/Inhibit SOCS3/activate STAT3	Increase tumor size, microvessels, and lymphatic vessels	Ying et al. (2016)
miR-940	Ovarian Cancer	Macrophages	M2 polarization	Promote proliferation and migration	Chen et al. (2017)
miR-21-3p/miR-125b-5p/miR-181d-5p	Ovarian Cancer	Undifferentiated macrophages	M2 polarization/Suppress SOCS4/5/STAT3 pathway	Tumor progression	Chen et al. (2018)
miR-1246	Ovarian Cancer	Macrophages	M2 polarization/Target Cav1/p-gp	Confer chemoresistance and tumor progression	Kanlikilicer et al. (2018)
	GOF Mutp53 Colon Cancer Cells	Macrophages	M2 polarization/TGF-β activation	Promote cancer progression and metastasis	Cooks et al. (2018)
	Hypoxic glioma	Macrophage	M2 polarization/target TERF2IP/activate the STAT3 signaling/inhibit the NF-κB signaling	Formation of the immunosuppressive microenvironment	Qian et al. (2020)
miR-23a-3p	Tunicamycin treated HCC cells	Macrophages	Elevate PD-L1 in macrophages/inhibit T-cell function through PTEN-AKT pathway	Tumor cells escape from antitumor immunity	Liu et al. (2019)
miR-130/miR-33	Breast cancer	M2 macrophages/TAMs	Transform M2 to M1 phenotype	Inhibit tumor progression	Moradi-Chaleshtori et al. (2021b); Moradi-Chaleshtori et al., (2021a)
TU339	Hepatocellular carcinoma	Macrophages	M1/M2 polarization/regulate pro-inflammatory cytokine/co-stimulatory molecule expression/phagocytosis	Regulate cell proliferation	Li et al. (2018)
RPPH1	Colorectal cancer	Macrophages	M2 polarization/induce EMT; interact with TUBB3; prevent ubiquitination	Promote metastasis and proliferation	Liang et al. (2019)
BCRT1	MDA-MB-231	Macrophages	M2 polarization/modulate migration ability and chemotaxis of macrophages	Promote cell migration and angiogenesis	Liang et al. (2020)
SOX2-OT	NSCLC	Macrophages	miR-627-3p/Smad axis	Enhance the EGFR-TKI resistance	Zhou et al. (2021)
CircASAP1	Hepatocellular carcinoma	Macrophages	Tams infiltration/regulate miR-326/miR-532-5p-MAPK1 signaling/miR-326/miR-532-5p-CSF-1 pathway	Promote cell proliferation and invasion	Hu et al. (2019)
circ_00074854	HCC cell	Macrophages	Suppress M2 polarization	Inhibit migration and invasion	Wang et al. (2021)
circ_0044516	Prostate cancer	—	Downregulate miR-29a-3p expression	Promote proliferation and metastasis	Li et al. (2020)
circ-RanGAP1	Gastric cancer	—	miR-877-3p/VEGFA axis	Promotes progression	Lu et al. (2020)
Cdr1	Ovarian cancer	—	miR-1270/SCAI signaling pathway	sensitize ovarian cancer to cisplatin	Zhao et al. (2019)
circRNAs_102481	NSCLC	—	miRNA-30a-5p/ROR1 axis	Contribute to EGFR-TKIs resistance	Yang et al. (2021)
Arachidonic Acid	Aspc-1	Macrophages	M2-like phenotype/PGE2 secretion, increased secretion of pro-tumoral, bioactive molecules	Contribute to tumor progression	(Linton et al., 2018)