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Identifier	000412853
Title	Autophagy orchestrates the regulatory program of tumor-associated myeloid-derived suppressor cells
Alternative Title	Η αυτοφαγία οργανώνει την κατασταλτική δράση των κατασταλτικών κυττάρων μυελικής σειράς στο περιβάλλον του όγκου
Author	Μπαρούνη, Ρόζα-Μαρία
Thesis advisor	Βεργίνης, Παναγιώτης
Reviewer	Σιδηρόπουλος, Πρόδρομος Μπερτσιάς, Γεώργιος
Abstract	Tumor cells are characterized by specific biologic properties, which help them not only to survive and proliferate uncontrollably, but also to evade the immunosurveillance. In particular, a well characterized mechanism, used by tumor cells, is the induction of immunosuppressive cells. In other words, in the tumor microenvironment, the differentiation of an heterogeneous population, called Myeloid Derived Suppressor Cells (MDSCs), is disrupted and, thus, results in the development of pathogenic MDSCs, which contribute to the immune system suppression, and specifically in the suppression of T cells. However, the mechanisms of MDSCs mediated tumor evasion remain elusive. In this project, we identify autophagy as a crucial pathway for MDSC-mediated suppression of anti-tumor immunity. Specifically, MDSCs in mouse tumors and melanoma patients showed increased levels of the autophagy pathway. Depletion of autophagy in myeloid compartment reduced the tumor size and enhanced the anti-tumor immune responses. Interestingly, monocytic MDSCs (M-MDSCs) exhibited impaired suppressive function both in in vitro and in vivo experiments. RNAseq of M-MDSCs, lacking the autophagy pathway showed significant differences in genes related to antigen presentation and lysosomal function. Also, autophagy-deficient M-MDSCs exhibited impaired lysosomal degradation and elevated levels of STAT1 that enhanced class II transactivator (CIITA) and MHC class II expression. Our findings depict autophagy as a novel molecular target of MDSC-mediated suppression of anti-tumor immunity.
Language	English
Subject	Cancer
	Καρκίνος
Issue date	2017-12-12
Collection	School/Department--School of Medicine--Department of Medicine--Post-graduate theses
	Type of Work--Post-graduate theses
Permanent Link	https://elocus.lib.uoc.gr//dlib/8/1/4/metadata-dlib-1512120006-515258-14207.tkl
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