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Veronica Huber, … , Monica Rodolfo, Licia Rivoltini
Published September 27, 2018
Citation Information: J Clin Invest. 2018;128(12):5505-5516. https://doi.org/10.1172/JCI98060.
Citation Information: J Clin Invest. 2018;128(12):5505-5516. https://doi.org/10.1172/JCI98060.
Abstract
The accrual of myeloid-derived suppressor cells (MDSCs) represents a major obstacle to effective immunotherapy in cancer patients, but the mechanisms underlying this process in the human setting remain elusive. Here, we describe a set of microRNAs (miR-146a, miR-155, miR-125b, miR-100, let-7e, miR-125a, miR-146b, miR-99b) that are associated with MDSCs and resistance to treatment with immune checkpoint inhibitors in melanoma patients. The miRs were identified by transcriptional analyses as being responsible for the conversion of monocytes into MDSCs (CD14+HLA-DRneg cells) mediated by melanoma extracellular vesicles (EVs) and were shown to recreate MDSC features upon transfection. In melanoma patients, these miRs were increased in circulating CD14+ monocytes, plasma, and tumor samples, where they correlated with the myeloid cell infiltrate. In plasma, their baseline levels clustered with the clinical efficacy of CTLA-4 or programmed cell death protein 1 (PD-1) blockade. Hence, MDSC-related miRs represent an indicator of MDSC activity in cancer patients and a potential blood marker of a poor immunotherapy outcome.
Authors
Veronica Huber, Viviana Vallacchi, Viktor Fleming, Xiaoying Hu, Agata Cova, Matteo Dugo, Eriomina Shahaj, Roberta Sulsenti, Elisabetta Vergani, Paola Filipazzi, Angela De Laurentiis, Luca Lalli, Lorenza Di Guardo, Roberto Patuzzo, Barbara Vergani, Elena Casiraghi, Mara Cossa, Ambra Gualeni, Valentina Bollati, Flavio Arienti, Filippo De Braud, Luigi Mariani, Antonello Villa, Peter Altevogt, Viktor Umansky, Monica Rodolfo, Licia Rivoltini
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Citation information
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microRNAs Shape Myeloid Cell-Mediated Resistance to Cancer Immunotherapy
E Daveri, E Vergani, E Shahaj, L Bergamaschi, SL Magra, M Dosi, C Castelli, M Rodolfo, L Rivoltini, V Vallacchi, V Huber |
Frontiers in immunology | 2020 |
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miR-21a in exosomes from Lewis lung carcinoma cells accelerates tumor growth through targeting PDCD4 to enhance expansion of myeloid-derived suppressor cells
X Zhang, F Li, Y Tang, Q Ren, B Xiao, Y Wan, S Jiang |
Oncogene | 2020 |
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The Influence of Tumor Microenvironment on Immune Escape of Melanoma
A Simiczyjew, E Dratkiewicz, J Mazurkiewicz, M Ziętek, R Matkowski, D Nowak |
International journal of molecular sciences | 2020 |
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Modulation of Immunosuppression by Oligonucleotide-Based Molecules and Small Molecules Targeting Myeloid-Derived Suppressor Cells
J Lim, A Lee, HG Lee, JS Lim |
Biomolecules and Therapeutics | 2020 |
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Melanoma-Derived Exosomal miR-125b-5p Educates Tumor Associated Macrophages (TAMs) by Targeting Lysosomal Acid Lipase A (LIPA)
D Gerloff, J Lützkendorf, RK Moritz, T Wersig, K Mäder, LP Müller, C Sunderkötter |
Cancers | 2020 |
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A Pilot Study Comparing the Efficacy of Lactate Dehydrogenase Levels Versus Circulating Cell-Free microRNAs in Monitoring Responses to Checkpoint Inhibitor Immunotherapy in Metastatic Melanoma Patients
MA Bustos, R Gross, N Rahimzadeh, H Cole, LT Tran, KD Tran, L Takeshima, SL Stern, S ODay, DS Hoon |
Cancers | 2020 |
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The miRNAs Role in Melanoma and in Its Resistance to Therapy
F Varrone, E Caputo |
International journal of molecular sciences | 2020 |
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Connections between Metabolism and Epigenetic Modification in MDSCs
H Dai, H Xu, S Wang, J Ma |
International journal of molecular sciences | 2020 |
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The role of cancer-derived microRNAs in cancer immune escape
M Yi, L Xu, Y Jiao, S Luo, A Li, K Wu |
Journal of Hematology & Oncology | 2020 |
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Long non-coding RNA LINC00520 promotes the proliferation and metastasis of malignant melanoma by inducing the miR-125b-5p/EIF5A2 axis
W Luan, Y Ding, H Yuan, S Ma, H Ruan, J Wang, F Lu, X Bu |
Journal of Experimental & Clinical Cancer Research | 2020 |
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The potential role of tumor-derived exosomes in diagnosis, prognosis, and response to therapy in cancer
M Czystowska-Kuzmicz, TL Whiteside |
Expert Opinion on Biological Therapy | 2020 |
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Targeted delivery of miR-99b reprograms tumor-associated macrophage phenotype leading to tumor regression
L Wang, YY Hu, JL Zhao, F Huang, SQ Liang, L Dong, Y Chen, HC Yu, J Bai, JM Yang, JY Fan, L Feng, SZ Li, H Han, HY Qin |
Journal for ImmunoTherapy of Cancer | 2020 |
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The tumour microenvironment shapes dendritic cell plasticity in a human organotypic melanoma culture
SD Blasio, GF van Wigcheren, A Becker, A van Duffelen, M Gorris, K Verrijp, I Stefanini, GJ Bakker, M Bloemendal, A Halilovic, A Vasaturo, G Bakdash, SV Hato, JH de Wilt, J Schalkwijk, IJ de Vries, JC Textor, EH van den Bogaard, M Tazzari, CG Figdor |
Nature Communications | 2020 |
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miR-146a-5p impairs melanoma resistance to kinase inhibitors by targeting COX2 and regulating NFkB-mediated inflammatory mediators
E Vergani, M Dugo, M Cossa, S Frigerio, LD Guardo, G Gallino, I Mattavelli, B Vergani, L Lalli, E Tamborini, B Valeri, C Gargiuli, E Shahaj, M Ferrarini, E Ferrero, MG Lira, V Huber, MD Vecchio, M Sensi, BE Leone, M Santinami, L Rivoltini, M Rodolfo, V Vallacchi |
Cell Communication and Signaling | 2020 |
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New Prognostic and Predictive Markers in Cancer Progression
S Costantini, A Budillon |
International journal of molecular sciences | 2020 |
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MicroRNAs as Key Players in Melanoma Cell Resistance to MAPK and Immune Checkpoint Inhibitors
ML Motti, M Minopoli, GD Carluccio, PA Ascierto, MV Carriero |
International journal of molecular sciences | 2020 |
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Advances in Natural or Synthetic Nanoparticles for Metastatic Melanoma Therapy and Diagnosis
MB Arasi, F Pedini, S Valentini, N Felli, F Felicetti |
Cancers | 2020 |
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Reconstruction of lncRNA-miRNA-mRNA network based on competitive endogenous RNA reveals functional lncRNAs in skin cutaneous melanoma
J Zhu, J Deng, L Zhang, J Zhao, F Zhou, N Liu, R Cai, J Wu, B Shu, S Qi |
BMC Cancer | 2020 |
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Resistance to PD-1/PD-L1 blockade cancer immunotherapy: mechanisms, predictive factors, and future perspectives
JY Sun, D Zhang, S Wu, M Xu, X Zhou, XJ Lu, J Ji |
Biomarker Research | 2020 |
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Stroke Exacerbates Cancer Progression by Upregulating LCN2 in PMN-MDSC
T Huang, Y Li, Y Zhou, B Lu, Y Zhang, D Tang, Y Gan, Z He, Z Chen, W Yu, P Li |
Frontiers in immunology | 2020 |
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Fighting infant infections with myeloid-derived suppressor cells
Victor Umansky, Rebekka Weber |
Journal of Clinical Investigation | 2019 |
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Myeloid-Derived Suppressor Cells: Ductile Targets in Disease
FM Consonni, C Porta, A Marino, C Pandolfo, S Mola, A Bleve, A Sica |
Frontiers in immunology | 2019 |
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Melanoma and Vitiligo: In Good Company
CM Failla, ML Carbone, C Fortes, G Pagnanelli, S DAtri |
International journal of molecular sciences | 2019 |
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Modulation of NK cells with checkpoint inhibitors in the context of cancer immunotherapy
B Sanchez-Correa, N Lopez-Sejas, E Duran, F Labella, C Alonso, R Solana, R Tarazona |
Cancer Immunology, Immunotherapy | 2019 |
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Role of miRNAs in Melanoma Metastasis
A Gajos-Michniewicz, M Czyz |
Cancers | 2019 |
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Targeting Myeloid Cells in Combination Treatments for Glioma and Other Tumors
AS Ding, D Routkevitch, C Jackson, M Lim |
Frontiers in immunology | 2019 |
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Noncoding RNAs Act as Tumor-Derived Molecular Components in Inducing Premetastatic Niche Formation
Z Zhang, J Qiao, D Zhang, W Zhu, J Zhu, X Leng, S Li |
BioMed Research International | 2019 |
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Extracellular vesicles, news about their role in immune cells: physiology, pathology and diseases
J Meldolesi |
Clinical & Experimental Immunology | 2019 |
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MicroRNA-92 expression in CD133+ melanoma stem cells regulates immunosuppression in the tumor microenvironment via integrin-dependent activation of TGF-β
C Shidal, NP Singh, P Nagarkatti, M Nagarkatti |
Cancer research | 2019 |
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MicroRNA networks regulate the differentiation, expansion and suppression function of myeloid-derived suppressor cells in tumor microenvironment
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Journal of Cancer | 2019 |
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Circulating biomarkers predictive of tumor response to cancer immunotherapy
EY Lee, RP Kulkarni |
Expert Review of Molecular Diagnostics | 2019 |
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The role of microvesicles containing microRNAs in vascular endothelial dysfunction
Z Shu, J Tan, Y Miao, Q Zhang |
Journal of Cellular and Molecular Medicine | 2019 |
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MicroRNA heterogeneity in melanoma progression
A Thyagarajan, KY Tsai, RP Sahu |
Seminars in Cancer Biology | 2019 |
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Role of microRNAs in remodeling the tumor microenvironment (Review)
Z Pan, Y Tian, G Niu, C Cao |
International journal of oncology | 2019 |
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Expression and predictive value of miR-489 and miR-21 in melanoma metastasis
H Mo, J Guan, ZC Yuan, X Lin, ZJ Wu, B Liu, JL He |
World journal of clinical cases | 2019 |
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A method for semi-automated image analysis of HLA class I tumour epithelium expression in rectal cancer
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European Journal of Histochemistry : EJH | 2019 |
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Nature reviews. Cancer | 2019 |
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Immunosuppressive circuits in tumor microenvironment and their influence on cancer treatment efficacy
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Virchows Archiv | 2018 |
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Pulmonary surfactant: an immunological perspective
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Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology | 2009 |
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