Abstract

In this PhD thesis, we mainly focused on the immunosuppressive aspects of the tumor micro-environnement (TME), more specifically on myeloid-derived suppressor cells (MDSCs). It is becoming increasingly clear that MDSCs hamper anti-tumor immune responses across different tumor types. Using multiple platforms, we generated mouse in vitro MDSCs and provided a proof-of-concept that the generated MDSCs resembled those found within the TME. Additionally, targeting these MDSCs was shown to be predictive for the outcome in tumor-bearing mice. Furthermore, we demonstrated that depletion of L-arginine by Arg-1+ MDSCs, as is the case in the TME, contributes to enhanced protection of tumor cells to irradiation. Simultaneously, we provided a proof-of-concept of the potential to identify new targets using our in vitro-generated mouse MDSCs. Perforin and granzyme B were shown, for the first time, to be present on MDSCs of mouse and human origin.
Although the availability of a platform to generate mouse MDSCs is of high importance, it would be even more substantial to translate this into a human setting. Therefore, we validated different human precursor cells as a starting point for MDSC cultures using a similar differentiation strategy as proven successful in the murine setting.
To conclude, we made considerable advances in the field of MDSC research by developing an in vitro MDSC platform that allows in depth analysis of these MDSC’s biology and strategies to manipulate these cells, thereby enhancing both basic and applied immunological research.
Date of Award19 Dec 2018
Original languageEnglish
Awarding Institution
  • Vrije Universiteit Brussel
SupervisorKarine Breckpot (Promotor), Mark De Ridder (Promotor), Jo Van Ginderachter (Jury), Eline Menu (Jury), Bart Neyns (Jury), Evelien Smits (Jury) & Grazyna Kochan (Jury)

Keywords

  • Myeloid-derived suppressor cell
  • Colorectal Cancer
  • tumor

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