Cancer creates a highly immunosuppressive environment, driven in part by the pathological activation of myeloid-derived suppressor cells (MDSCs), which suppress anti-tumor immunity through immunosuppressive pathways. Specific microRNAs, such as miR-146a and miR-155, play a key role in the generation of immunosuppressive MDSCs. Elevated levels of these microRNAs in cancer patients plasma are linked to resistance to immunotherapy. Experimental evidence demonstrates that specific microRNAa can convert normal monocytes into MDSCs in vitro, while their inhibition using enables the reprogramming of these cells towards immunogenic profiles.
This PhD project will explore cutting-edge nanotechnology by employing polylactide-co-glycolide nanoparticles loaded with miRNA agonists and antagonists to reprogram MDSCs. The work will initially focus on ex vivo models, where MDSCs differentiated from healthy donor peripheral blood mononuclear cells will be characterized phenotypically and functionally. The reprogramming potential of nanoparticles will be evaluated based on changes in MDSC phenotype, gene expression, and functional properties such as suppression of T/NK cell activity. Subsequent experiments will include 2D and 3D co-cultures of melanoma patient-derived MDSCs with cancer cells to assess nanoparticle-induced effects on tumor suppression.
This interdisciplinary research provides training opportunities in advanced cellular technologies, multicolor flow cytometry, and secretome profiling, with potential internships at ERA4Health partner institutions.
Mokslinis vadovas / Supervisor: Dr. Agata Mlynska
Kontaktai / Contacts:
tel. / phone: +370 67734601
Programme: Biology N 010