MiRNAs at the Crossroads between Innate Immunity and Cancer: Focus on Macrophages
Abstract
:1. Introduction
1.1. MiRNA Biogenesis and Maturation: A Brief Overview
1.2. Dysregulation of miRNA Expression and Biogenesis in Cancer
1.2.1. Amplification and Deletion of miRNA Genes
1.2.2. Epigenetic Alterations
1.2.3. Defects in the miRNA Biogenesis Pathway
1.2.4. Mutations of miRNA Target Genes
2. Role of miRNAs in Macrophage Polarization
3. The Fine Balance of the Innate Immune Tumor Response
4. miRNAs Involved in Tumor Immunosurveillance
5. TAM-Derived miRNAs in Cancer-Related Inflammation
6. Exosome-Derived miRNAs in Cancer Progression and Metastasis
7. Immunogenic Cell Death: A Promising Tool for Anti-Cancer Immunotherapy
miRNAs as Therapeutic Agents in Cancer Treatment
8. Conclusions
Acknowledgments
Conflicts of Interest
References
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miRNA | Expression | Targets | Phenotype | |
---|---|---|---|---|
miR-155 | ↑ M1 macrophages | C/EBPβ, SHIP1, IL13Rα1, SMAD2/3 | Reprograms pro-tumoral M2/TAM macrophages to M1 pro-inflammatory macrophages | Macrophage Polarization |
miR-125b | ↑ M1 macrophages | IRF4 | ↑ responsiveness to IFNγ ↑ tumor killing | |
miR-127 | ↑ in M2 macrophages ↓ by inflammation | DUSP1 | ↑ M1- and ↓ M2-related genes | |
miR-146a | ↑ M2 macrophages | NOTCH1, INHBA, PPARγ, | ↑ M2 polarization and inflammation ↓ M1 polarization | |
miR-223 | ↓ TAM | IL1β, IL-6 | ↑ M2 polarization | |
let-7c | ↑ in M2 macrophages ↓ by inflammation | C/EBPδ, PAK1 | ↑ M2- and ↓ M1-related genes | |
miR-511-3p | ↑ TAM | ROCK2 | ↓ pro-tumoral gene signature of TAMS and ↓ tumor growth | Tumor invasion |
miR-155 | ↑ M1 macrophages | SHIP1 | ↑ anti-tumor immunity. MiR-155 KO myeloid cells induce faster tumor growth | |
miR-155 | ↑ MDSC | SOCS1 | Required for tumor growth and the generation of CD4+ Treg cells. MiR-155 KO mice are resistant to carcinogenesis | Immune suppression (MDSC) |
miR-494 | ↑ MDSC | PTEN | Regulates cell cycle progression; it induces arrest in G2/M and increased inflammation | |
miR-20a | ↑ MDSC | STAT3 | ↓ MDSC-dependent suppression of CD4+ and CD8+ T cell response | |
miR-223 | ↓ MDSC | MEF2C | Suppresses differentiation of tumor induced- CD11bGr1+MDSC | |
miR-21 | ↑ MDSC | SHIP1 | ↑ proliferation and survival | |
miR-690 | ↑ MDSC | C/EBPα | ↑ MDSC expansion and proliferation ↓ terminal differentiation | |
miR-17-5p | ↑ MDSC | STAT3 | ↓ MDSC ability to suppress Ag-specific CD4+ and CD8+ T cell response |
miRNA | Donor Cells | Recipient Cells | Phenotype | |
---|---|---|---|---|
miR-21 | TAM | gastric cancer cells | ↑ cell proliferation ↓ chemosensitivity and apoptosis | TAM-derived exosomal miRNAs |
miR-223 | TAM | breast cancer cells | ↑ cell migration capacity and invasiveness | |
miR-9 | TAM | endothelial cells | ↑ cell migration and angiogenesis | |
miR-940 | epithelial ovarian cancer | TAM | ↑ M2 polarization | Tumor-secreted exosomal miRNAs |
miR-203 | colorectal carcinoma | monocytes | ↑ M2 polarization | |
miR-21 | solid tumor cells | macrophages | ↑ proliferation, survival, invasion and migration | |
miR-29b | solid tumor cells | macrophages | OncomiR: ↑ secretion of pro-metastatic and pro-inflammatory cytokines | |
miR-9 | tumor cell lines | cancer cells | OncomiR: ↑ endothelial cell migration ↑ tumor angiogenesis | |
miR-210 | breast cancer cells | adjacent cancer cells | OncomiR: ↑ angiogenesis | |
miR-105 | breast cancer cells | endothelial cells of distant organs | OncomiR: ↑ metastasis and vascular permeability by targeting the tight junction protein ZO-1 | |
miR-200 | metastatic cancer cells | metastatic cancer cells | Regulates mesenchimal to epithelial transition | |
let-7e | gastric cancer cells | cancer cells | Tumor suppressor function (i.e., inhibits metastasis) | |
miR-23b | bladder carcinoma cells | cancer cells | Tumor suppressor function (e.g., inhibition angiogenesis, invasion and metastasis) | |
miR-224 | bladder carcinoma cells | cancer cells | Tumor suppressor functions (e.g., inhibition angiogenesis, invasion and metastasis) | |
miR-921 | bladder carcinoma cells | cancer cells | Tumor suppressor functions (e.g., inhibition angiogenesis, invasion and metastasis) | |
miR-15a | mesenchymal stromal cells | myeloma cells | Tumor suppressor function |
Immunological Target | Drug Name | Characteristics | Clinical Phase Testing | |
---|---|---|---|---|
Drugs blocking Immune Checkpoints | anti-CTLA4 | IPILIMUMAB | fully human IgG1 | approved, advanced melanoma |
TREMELIMUMAB | fully human IgG2 | failed phase III trial melanoma | ||
anti-PD1 | NIVOLUMAB | fully human IgG4 | approved, melanoma, squamous NSCLC | |
PEMBROLIZUMAB | fully human IgG4 | approved, melanoma | ||
PIDILIZUMAB | humanized IgG1 | phase I-II trial | ||
anti-PD-L1 | BMS-936559 | fully human IgG4 | phase I trial | |
MSB0010718C | fully human IgG1 | phase I-II trial | ||
MEDI4736 | Fc-modified human IgG1 | phase I-III trial | ||
MPDL3280A | Fc-modified human IgG1 | phase I-III trial | ||
CAR T cells therapy | anti-CD19 | TISAGENLECLEUCEL-T (KimryahTM) | chimeric antigen receptor T cells | approved, Acute lymphatic leukemia |
AXICABTAGENE CILOLEUCEL (YescartaTM) | chimeric antigen receptor T cells | approved, B cell lymphoma | ||
anti-CD20 | NCT01735604 | chimeric antigen receptor T cells | phase I trial, progressive malignant lymphoma | |
anti-CD30 | NCT02259556 | chimeric antigen receptor T cells | phase II-III trial, Hodgkin lymphoma | |
anti-EGFR | NCT01869166 | chimeric antigen receptor T cells | phase II-III trial, Advanced lung cancer | |
miRNA-based drugs | miR-34 | MRX34 | miRNA mimic | phase I trial, advanced hepatocarcinoma |
miR-122 | MIRAVIRSEN | LNA-based antimiRNA | phase II trial, HCV | |
miR-29b | MRG-201 | miRNA mimic | phase I trial, fibrotic diseases | |
miR-155 | MRG-106 | AntimiRNA | phase I trial, hematological malignances | |
miR-10b | - | AntimiRNA | preclinical phase, glioblastoma | |
miR-221 | - | AntimiRNA | preclinical phase, hepatocarcinoma |
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Curtale, G. MiRNAs at the Crossroads between Innate Immunity and Cancer: Focus on Macrophages. Cells 2018, 7, 12. https://doi.org/10.3390/cells7020012
Curtale G. MiRNAs at the Crossroads between Innate Immunity and Cancer: Focus on Macrophages. Cells. 2018; 7(2):12. https://doi.org/10.3390/cells7020012
Chicago/Turabian StyleCurtale, Graziella. 2018. "MiRNAs at the Crossroads between Innate Immunity and Cancer: Focus on Macrophages" Cells 7, no. 2: 12. https://doi.org/10.3390/cells7020012