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Identifier

000390076

Title

Investigate the role of autophagy in the Myeloid Derived Suppressor Cells -mediated tolerance of anti-tumor responses

Alternative Title

Μελέτη του ρόλου της αυτοφαγίας στην ανοσολογική ανοχή που επάγεται απο τα κατασταλτικά κύτταρα της μυελικής σειράς στις αντικαρκινικές αποκρίσεις

Author

Μίντζας, Κωνσταντίνος

Thesis advisor

Βεργίνης, Παναγιώτης

Reviewer

Μπούμπας, Δημήτριος
Χαμηλός, Γεώργιος

Abstract

Recruitment of suppressive immune cell types in tumor sites is a major manifestation of tumor tolerance. Myeloid-derived suppressor cells (MDSCs) play a very important role in the suppression of anti-tumor immunity by expressing several suppressive molecules and by expanding regulatory T cells. However, the exact molecular mechanism of MDSCs-Treg interaction is not yet fully understood. Autophagy, apart from its homeostatic role, has been implicated in antigen presentation through MHC class II molecules in antigen-presenting cells, but its implication in regulatory T cell expansion by MDSCs has not been studied. In this study, we observed an expansion of MDSCs in tumor-bearing mice that is accompanied by an increase in the expression of the autophagy-related genes Atg5 and Bcl1. Mice with a conditional knock-out of Atg5 gene in myeloid cells (LysMcreAtg5fl/fl) showed decreased tumor growth compared to control tumor-bearing mice. Furthermore, LysMcreAtg5fl/fl mice showed a markedly expansion of MDSCs in spleen compared to control mice and a differential expression of several effector molecules (TGFβ, arginase-1 and CEBP/β) in these cells. Collectively, these results support an important role for autophagy in the function of myeloid cells and additional experiments will elucidate the molecular mechanism underlying tumor tolerance by MDSCs.

Language

English

Subject

Autophagy

Cancer

Suppressor cells

Tolerance

Ανοσολογική ανοχή

Αυτοφαγία

Καρκίνος

Κατασταλτικά κύτταρα

Issue date