Malignant melanoma remains a disease with a dismal prognosis due to the poor response to currently available therapies. Melanoma immune escape is mediated by different mechanisms dealing, in particular, with a rapid recruitment, expansion and activation of myeloid-derived suppressor cells (MDSCs), representing a heterogeneous population of immature myeloid cells that an strongly inhibit T-cell mediated anti-tumor reactivity. Moreover, melanoma progression is characterized by an increased production of various factors needed to drive MDSC migration and to keep their suppressive phenotype including IL-1, VEGF, IL-6, and GM-CSF. Using the ret transgenic mouse model of spontaneous melanoma, we revealed a remarkable elevation of MDSC frequencies in melanoma lesions. Recent publications reported on the tumor infiltration by neutrophils or their accumulation in the peripheral blood of melanoma patients associated with poor prognosis. However, the differential migration of various subsets of MDSCs and neutrophils in primary and metastatic melanoma lesions was not investigated.
The goal of the project is to study the differences in the recruitment and functional impact of monocytic and polymorphonuclear MDSCs in primary tumor and metastatic lesions in ret transgenic mice and melanoma patients. In parallel the accumulation of neutrophils in tumor-bearing mice and melanoma patients will be studied. We plan to discover new molecular targets on neutrophils and MDSC that are needed for the design of novel therapeutic strategies to neutralize immunosuppression mediated by these cells to increase anti-cancer responses. In addition, the effect of patients’ therapy with negative checkpoint inhibitors on neutrophils and MDSCs will be analyzed.
This project is supported by the DKFZ/Israel Cooperation Program in Cancer Research and will be performed at the Clinical Cooperation Unit Dermato-Oncology in the University Medical Center Mannheim.
Diploma thesis in biology or Master degree; experience in work with mice is desirable but not mandatory.
Methods: Basic immunological (flow cytometry, ELISA, ELISPOT, tetramer staining, immunohistochemistry) and molecular biological (PCR, RT-PCR, Western Blot) techniques, work with genetically modified mice.
Interessanten, vielseitigen Arbeitsplatz
Vergütung nach TV-L
Möglichkeiten zur Teilzeitarbeit
Gute Fort- und Weiterbildung
as soon as possible
The position is for the PhD student (PhD Fellowship) for 3 years.
Prof. Dr. Viktor Umansky
phone +49 621 383-3773
Deadline: September 13, 2017