BJMO - volume 15, issue 3, may 2021
J.R.M. Van Audenaerde PhD, G. Roeyen MD, PhD, M. Peeters MD, PhD, E.L.J.M Smits PhD
Pancreatic Ductal Adenocarcinoma (PDAC) has the worst 5-year survival of all cancer types. Treatment options for these patients are limited and consist mainly of chemotherapy. However, the unique tumour microenvironment with its dense, fibrotic shield causes resistance to current and novel therapies. Tackling this stromal shield is therefore deemed crucial for making progress in PDAC treatment. We investigated in this thesis the potential of Natural Killer (NK) cells to address this high medical need. Firstly, our systematic review revealed strong evidence of their importance in PDAC and how the tumour renders them into a suppressed and less functional state. Based on this information, we sought to stimulate NK cells in such way that they attack both tumour and surrounding stroma. We show that, upon stimulation with IL-15, NK cells are capable of killing both pancreatic cancer and stellate cells, the drivers of the stromal reaction, in a contact-dependant manner. Increased expression of NKG2D and TIM-3 receptors was partially responsible for this enhanced killing. Furthermore, in our search to potentiate IL-15 stimulation, we combined this with an immune priming CD40 agonist and demonstrated profound anti-tumour effects and prolonged survival in PDAC mouse models. Increased intra-tumoral cytotoxic T cells, NK cells and reduced T regulatory cells combined with increased cross-presenting dendritic cells in the tumour draining lymph nodes are the main effectors of the observed anti-tumour effects. Summarised, our data provide a strong rationale for NK cell-driven cancer immunotherapy where immune stimulation is combined with immune priming. Initiation of an early-phase clinical trials with this novel combination immunotherapy for PDAC patients is warranted.
BELG J MED ONCOL 2021;15(3):128-31Read more
BJMO - volume 15, issue 1, january 2021
L. Sorber PhD, K. Zwaenepoel PhD, J. Jacobs PhD, C. Rolfo MD, PhD, G. Roeyen MD, PhD, P. Pauwels MD, PhD
The general aim of this thesis was to determine the optimal workflow of circulating cell-free nucleic acid- (cfNA) based liquid biopsy for implementation in routine clinical practice. We started by evaluating several pre-analytical variables of the liquid biopsy workflow. We examined several cfDNA isolation kits, determined the optimal centrifugation protocol for both cfDNA and cfRNA, and determined the cfDNA stabilising efficiency of (specialised) blood collection tube (BCT). Next, we focused on the clinical applicability of liquid biopsy in non-small cell lung cancer (NSCLC). Based on this work, we specified recommendations regarding (pre-) analytical and biological variables to ensure successful liquid biopsy analysis.
(BELG J MED ONCOL 2021;15(1):48-50)Read more
BJMO - 12, issue 3, february 2018
T. Vandamme MD, PhD, W. Lybaert MD, Marc Simoens , Wim Demey MD, T. Rondou , P. Abrams , C. Mattelaer , B. Op de Beeck , O. D’Archambeau , G. Roeyen MD, PhD, Lesley De Backer , Marc Peeters , Steering Committee , NET-specialists
BJMO - 2017, issue 3, february 2017
W. Lybaert MD, T. Vandamme MD, PhD, M. Simoens , I. Dero MD, Wim Demey MD, T. Rondou , A. Cuypers , P. Abrams , C. Mattelaer , A. Driessen MD, PhD, B. Op de Beeck , O. D’Archambeau , G. Roeyen MD, PhD, L. De Backer , M. Peeters MD, PhD, NET specialists NETwerk Steering Committee