Table 1.

Effect of tumor-derived extracellular vesicles on the macrophages in the tumor microenvironment.

Cancer Type	Cellular Source	Vesicular Cargo	The Main Result	Refs.
Breast cancer	MCF10A MCF10AT MCF10CA1a MDA-MB-231	Anx II	Activated NF-B, p38MAPK, and STAT3 pathways in macrophages, leading to increased IL-6 and TNF-α secretion	[31]
	C57BL/6 EO771	gp130	Caused macrophages to shift from a normal to a polarized phenotype such as TAM via activation of the IL-6 response pathway and STAT3.	[28]
	4T1	miR-125b-1-3p, miR-100-5p, and miR-183-5p	Inhibited the expression of PPP2CA, which could promote the release of pro-inflammatory cytokines such as IL-1b, IL-6, and TNF-a from macrophages stimulating tumor invasion.	[20]
	MDA-MB-231	Vesicular CD63 protein	Polarized and activated macrophages, in which CD206 (a marker for M2) was expressed more than NOS2 (a marker for M1).	[36]
Prostate cancer	PC3	miRNA Let-7b	Prostate-derived extracellular vesicles had more miRNA Let-7b than cellular miRNA Let-7b can lead to macrophage polarization.	[37]
Lung cancer	A549	Vesicular cargoes	Altered transcriptomic and bioenergetic profiles of macrophages, forced them to polarize to an M2 phenotype.	[38]
	NCI-H1437 NCI-H1792 NCI-H2087	miR-103a	Polarized monocytes toward immunosuppressive M2-type macrophages.	[39]
	A549 H1299	Vesicular cargoes	Enhanced the levels of MMP2, MMP9 CD163, TNF-, IL-8, IL-6, and IL-10 and decreased expression of iNOS which led macrophages to exhibit a dual M1/M2 phenotype	[40]
	A549 H1299	Vesicular PRPS2	Induced M2 polarization and led to drug resistance of cancer cells.	[41]
Hepatocellular carcinoma (HCC)	PLC/PRF/5	Long non-coding RNAs (lncRNA) TUC339	Caused macrophage polarization to be more immunosuppressive.	[42]
	Hepa1-6 H22	miR-146a-5p	Enhanced M2 polarization by triggering NF-B signaling and producing pro-inflammatory proteins	[34]
Colorectal cancer(CRC)	DLD-1	miR-145	Induced M2 polarization via upregulation of IL-10 and downregulation of HDAC11.	[43]
	Blood samples from CRC patients HCT116 HT29	miR-106b	Contributed to M2 polarization of macrophages via significant increase in the miR-106b level in macrophages. It directly suppressed programmed cell death 4 (PDCD4) at a post-transcription level that led to an activated PI3Kγ, AKT, and mTOR signaling cascade.	[35]
	Blood samples from CRC patients HCT-8 LoVo HT-29 Caco-2	miR-934	Induced M2 macrophage polarization by activating the PI3K/AKT signaling pathway and downregulating PTEN.	[30]
	CT-26 SW620	Cytoskeleton-centric proteins	In macrophages, caused cytoskeleton reorganization via promoting elongation and F-actin polarization.	[44]
	Blood samples from CRC patients HCT116 DLD-1 HT29	miR-1246	Reprogrammed macrophages into the cancer-promoting state after macrophage uptake.	[45]
	Blood samples from CRC patients DLD1 HCT116 Lovo SW480 SW620 HT29 CaR-1 RKO Colo205 Colo320DM	miR-203	Promoted M2 polarization, which modulated liver metastasis of colon cancer cells.	[46]
Epithelial ovarian cancer	SKOV3	miR-21-3p, miR-181d-5p, and miR-125b-5p	Promoted M2 macrophage polarization results in epithelial ovarian cancer cell proliferation and migration under hypoxic circumstances.	[47]
Glioblastoma	GSC20 GSC276 U87	Vesicular cargoes	The presence of phospho-STAT3 in TEVs switched monocytes toward the tumor-supportive M2 phenotype	[33]
	U87MG SBN19 U251	FasL, TRAIL, CTLA-4, CD39, and CD73	Promoted M2 polarization by activating the NF-κB pathway in macrophages	[48]
	U251	Vesicular cargo	Induced M2 polarization leading to tumor growth via promoting TAM Arginase-1+ exosome secretion	[49]
Oral squamous cell carcinoma	SCC-9 CAL-27	miR-29a-3p	Targeted macrophages directly, and activated p-STAT1 to promote M2 expression	[32]
	Cal-27	CMTM6	Delivered CMTM6 to macrophages and induced M2-like macrophage polarization by activating ERK1/2 signaling	[29]
Ovarian cancer	Blood samples from overian cancer patients Skov3 A2780	miR-222	Induced M2 polarization of macrophages by activating STAT3 pathway	[50]