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Prof. Dr. Viktor Umansky

Our group is focused on the study of mechanisms of immunosuppression in melanoma microenvironment mediated by myeloid-derived suppressor cells (MDSC). Using RET transgenic melanoma mouse model and samples from melanoma patients undergoing immunotherapy, we found an enrichment and stimulation of MDSC that correlated with melanoma progression and worse clinical outcome.

We study i) mechanisms of MDSC activation by IL-6 and their recruitment to the tumor by CCR5/CCR5 ligand interactions; ii) conversion of normal myeloid cells into MDSC by melanoma-derived extracellular vesicles (EV) via toll-like receptor (TLR) signaling and microRNA transfer or induction; and iii) contribution of MDSC subsets (polymorphonuclear vs. monocytic MDSC) to immunosuppression and melanoma metastasis. Approaches for MDSC targeting are under investigation to improve melanoma immunotherapy.

Publications

  1. Fleming V, Hu X, Weller C, Weber R, Groth C, Riester Z, Hüser L, Sun Q, Nagibin V, Kirschning C, Bronte V, Utikal J, Altevogt P, Umansky V. Melanoma Extracellular Vesicles Generate Immunosuppressive Myeloid Cells by Upregulating PD-L1 via TLR4 Signaling. Cancer Res. 2019, 79: 4715-4728.
  2. Huber V, Vallacchi V, Fleming V, Hu X, Cova A, Dugo M, Shahaj E, Sulsenti R, Vergani E, Filipazzi P, De Laurentiis A, Lalli L, Di Guardo L, Patuzzo R, Vergani B, Casiraghi E, Cossa M, Gualeni A, Bollati V, Arienti F, De Braud F, Mariani L, Villa A, Altevogt P, Umansky V, Rodolfo M, Rivoltini L. Tumor-derived microRNAs induce myeloid suppressor cells and predict immunotherapy resistance in melanoma. J Clin Invest. 2018, 128: 5505-5516.
  3. Blattner C, Fleming V, Weber R, Himmelhan B, Altevogt P, Gebhardt C, Schulze TJ, Razon H, Hawila E, Wildbaum G, Utikal J, Karin N, Umansky V. CCR5+ Myeloid-Derived Suppressor Cells Are Enriched and Activated in Melanoma Lesions. Cancer Res. 2018, 78: 157-167.
  4. Bronte V, Brandau S, Chen SH, Colombo MP, Frey AB, Greten TF, Mandruzzato S, Murray PJ, Ochoa A, Ostrand-Rosenberg S, Rodriguez PC, Sica A, Umansky V, Vonderheide RH, Gabrilovich DI. Recommendations for myeloid-derived suppressor cell nomenclature and characterization standards. Nat Commun. 2016, 7: 12150.
  5. Gebhardt C, Sevko A, Jiang H, Lichtenberger R, Reith M, Tarnanidis K, Holland-Letz T, Umansky L, Beckhove P, Sucker A, Schadendorf D, Utikal J, Umansky V. Myeloid Cells and Related Chronic Inflammatory Factors as Novel Predictive Markers in Melanoma Treatment with Ipilimumab. Clin Cancer Res. 2015, 21: 5453-5459.

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