Table 1.
List of selected studies focused on EVs as biomarkers or prognostic factors with a description of their potential impact on the immune system.
| Number of Patients | Investigated Molecule in EVs | Observed Correlation | Potential Role in Cancer Immunology | Sample | Reference |
|---|---|---|---|---|---|
| 28 (20 with cc-RCC, 2 with p-RCC, 4 with ch-RCC, 2 with unknown type) |
GGT | Higher level and activity of GGT in EVs in patients with advanced disease and microvascular invasion |
May take part in T lymphocytes activation [98] | Serum | Horie et al. [89] |
| 70 with cc-RCC | miR-30c-5p | Biomarker of cc-RCC (downregulated in comparison to 30 HI)—sensitivity and specificity were 68.57% and 100%, respectively | miR-30c-5p directly inhibits HSPA5, which can be negatively associated with ferroptosis and autophagy activation [99,100]. HSPA5 is involved in UPR, which is important during tumor antigen presentation [101] | Urine | Song et al. [88] |
| 4 with cc-RCC | PTRF | Increased expression and secretion of PTRF in comparison to HI |
PTRF can be associated with higher expression of PD-L1 [102] | Urine | Zhao et al. [103] |
| 29 with cc-RCC | Proteomic analysis | 72/333 proteins were present only in cc-RCC patients (not in 23 HI) |
Complement components and antibodies chains present in EVs may be evidence of immune response against tumor | Urine | Raimondo et al. [104] |
| 22 (18 with cc-RCC, and 4 with p-RCC) | mi-RNA profile |
hsa-miR-149-3p and hsa-miR-424-3p were upregulated; hsa-miR-92a-1-5p were down-regulated |
miR-149-3p can promote EMT [105], miR-424 can decrease PD-L1 expression [106], miR-92a may be involved in IL-6 secretion [107] | Urine | Xiao et al. [108] |
| 77 with cc-RCC | CA-9 | Biomarker and prognostic factor of survival and recurrence | Expression of CA-9 can be associated with higher expression of PD-L1 [62] | Plasma | Vergori et al. [63] |
| 6 with cc-RCC | miRNA profile | Increased level of miR-224-5p | miR-224-5p inhibits the expression of CCND1, which increases PD-L1 protein abundance [109] | Urine | Qin et al. [109] |
| 13 (12 with cc-RCC, 1 with p-RCC) |
Mitochondrial genes HV1; CYB | Detection of metastasis and aggressiveness | They are a marker of increased ROS production which can modulate T lymphocytes survival [110] | Plasma | Arance et al. [111] |
| 32 with cc-RCC | hsa-miR-301a-3p; hsa-miR-1293 |
Decrease of hsa-miR-1293 and increase of hsa-miR-301a-3p were the biomarker of metastatic disease | miR-1293 regulates the expression of proteins involved in DNA repair processes [112], miR-301a is involved in T-lymphocytes accumulation and IFN-gamma production [113] | Plasma | Dias et al. [114] |
| 32 with localized cc-RCC and 23 with metastatic cc-RCC | TIMP-1 | Biomarker of tumor size and presence of metastasis | TIMP-1 can trigger NET formation [115], induces sensitivity to FAS-related apoptosis of cancer cells [116] | Plasma | Dias et al. [117] |
| 33 with cc-RCC | mRNA | Decreased levels of GSTA1, CEBPA, and PCBD1 mRNA | CEBPA can be involved in tumor-induced immunosuppression (by regulating the function of MDSCs) [118], GSTA1 is involved in ROS production, which can promote tumorigenesis and regulate T lymphocytes function [119,120], PCBD1– ND | Urine | De Palma et al. [121] |
| 6 with cc-RCC | mRNA | Decreased levels of NME2, AAMP, CAPNS1, VAMP8, and MYL12B mRNA | Nme2 can stimulate Tc lymphocytes [122], Aamp can polarize M population into M1 [123], Myl12b may be the ligand for CD69 (suppressor of anti-tumor immune response) [124], Vamp8, Capns1 ND | Urine | Marek-Bukowiec et al. [125] |
| 8 with cc-RCC | miRNA | Elevated level of miR-4525 | ND | Serum | Muramatsu-Maekawa et al. [126] |
| 9 with cc-RCC | mRNA | Presence of four types of mRNA (ALOX5, RBL2, VEGFA, TLK2) was specific for cc-RCC patients | ALOX-5 expressed by macrophages can be a precursor of pro-tumorigenic metabolites [127], RBL2, TLK2 regulate the cell division process [91], VEGFA pathway can stimulate the proliferation of tumor-induced T-regulatory lymphocytes [128] | Urine | Kuczler et al. [91] |
AAMP—Angio-associated migratory cell protein; ALOX5—Arachidonate 5-lipoxygenase; CA-9—Cancer antigen 9; CAPNS1—Calpain small subunit 1; cc-RCC—clear cell renal cell carcinoma; CCND1—Cyclin D1; CD—Cluster of differentiation; CEBPA—CCAAT/Enhancer binding protein alpha; ch-RCC—chromophobe renal cell carcinoma; CYB—Cytochrome B; DNA—Deoxyribonucleic acid; EMT—Epithelial-mesenchymal transition; EVs—Extracellular vesicles; FAS—Fas Cell Surface Death Receptor; GGT—Gamma-glutamyl transferase; GSTA1—Glutathione S-transferase A1; HI—Healthy individuals; hsa-miR—human microRNA; HSPA5—Heat shock protein A5; HV1—Hirudin variant 1; IFN—interferon; IL—interleukin; M—macrophages; M1—macrophage type 1; MDSCs—Myeloid derived suppressor cells; miR—microRNA; MYL12B—Myosin light chain 12B; NET—Neutrophil extracellular traps; NME2—Nucleoside diphosphate kinase B; p-RCC—papillary renal cell carcinoma; PCBD1—Pterin-4-alpha-carbinolamine dehydratase 1; PD-L1—Programmed death-ligand 1; PTRF—Polymerase and transcript release factor; RBL2—Retinoblastoma-like protein 2; ROS—Reactive oxygen species; TIMP-1—Tissue inhibitor of metalloproteinase 1; TLK2-Tousled-like kinase 2; UPR—Unfolded protein response; VAMP8—Vesicle associated membrane protein 8; VEGFA—Vascular Endothelial Growth Factor A.