Table 2.
In vitro and in vivo studies investigating miRNAs as therapeutic substances.
| miRNA | Tumor Type | Experimental Setting | Outcome | Author |
|---|---|---|---|---|
| miR-16 | Healthy tissue | Mouse model | M1 macrophage differentiation, T cell activation and downregulation of PD-L1 following viral miR-16 transfection |
Jia et al. [83] |
| Mesothelioma | Humans (phase I) | 3% PR, 55% SD with a miR-16 based mimic | Van Zandwijk. [78] | |
| miR-21 | Melanoma | Mouse model | Inhibition of M2 macrophage differentiation and increased tumor cell killing in combination with ICI in miR-21 deficient mice |
Xi et al. [84] |
| miR-28 | Melanoma | Mouse model | Restoration of T cell function and increased cytokine production following transfection with a miR-28 mimic | Li et al. [86] |
| miR-34a | Advanced tumors | Humans (Phase I) | 2% PR, 12% SD with a liposomal miR-34a mimic | Beg et al. [77] |
| miR-124 | Glioblastoma | Mouse model | Increased IFN-γ production by T cells following treatment with a miR-124 mimic | Wei et al. [92] |
| miR-138 | Glioblastoma | Mouse model | Decreased expression of T cell exhaustion markers following treatment with a miR-138 mimic | Wei et al. [93] |
| CRC | Mouse model | PD-L1 downregulation by miR-138-5p | Zhao et al. [94] | |
| miR-146a | Melanoma | Mouse model | Increased IFN-γ expression levels in miR-146a deficient mice Increased ICI sensitivity with combined miR-146a antagomiR treatment |
Mastroianni et al. [85] |
| miR-149-3 | TNBC | Mouse model | Reversal of T cell exhaustion and increased secretion of effector cytokines after transfection with a miR-149-3 mimic |
Zhang et al. [100] |
| miR-155 | Melanoma | Mouse model | miR-155 triggers M1 macrophage differentiation | Huffaker et al. [87] |
| DLBCL | In vitro | Increased sensitivity to ICI after transfection with a miR-155 mimic | Zheng et al. [102] | |
| miR-381-3p | NSCLC | Mouse model | Decreased CXCR4 expression and increased ICI sensitivity by miR-381-3p | Zhang et al. [88] |
| let-7a/b | HNSCC | Mouse model | CD8+ T cell infiltration and cytokine production by combining let-7a/b mimics with ICI | Yu et al. [97] |
| TNBC | Mouse model | Reversal of tumor-suppressive properties of TAMs following delivery of let-7b mimics | Huang et al. [101] |
CRC: colorectal cancer, DLBCL: diffuse large B cell lymphoma, HNSCC: head and neck squamous cell carcinoma, ICI: immune-checkpoint inhibitor, IFN-γ: interferon-γ, miR: microRNA, NSCLC: non-small cell lung cancer, PR: partial remission, SD: stable disease, TAMs: tumor-associated macrophages, TNBC: triple-negative breast cancer.