Title Promoter Affiliations Abstract "Getting real with response inhibition – characterizing pure inhibitory function in healthy participants and people with ADHD" "Nico Böhler" "Department of Experimental clinical and health psychology, Department of Experimental psychology" "Response inhibition is a crucial cognitive-control function, which is derailed in important clinical disorders. Typically, it is characterized using the Stop-signal task. Here, we highlight one largely ignored (but crucial) limitation to its interpretability (‘trigger failures’). We will systematically explore which factors determine their frequency, how to counteract their occurrence, and apply this to a highly relevant clinical group (ADHD)." "Molecular profiling of clear-cell renal cell carcinoma and prediction of response to targeted therapies against the vascular endothelial growth factor receptor, immune checkpoint inhibitors and mTOR inhibitors in the metastatic setting." "Benoit Beuselinck" "Laboratory of Experimental Oncology, Laboratory of Translational Genetics (VIB-KU Leuven)" "Over the last 10 years, several new therapies became available for the treatment of metastaticclear-cell kidney tumors: blood vessel inhibitors, mTOR-inhibitors and new generationimmunotherapy. Although these therapies have globally improved therapeutic outcome, individualpatient responses are highly variable. There is an urgent need to know in advance which therapywill be the best for each patient in order to improve therapeutic efficacy, prevent unnecessary sideeffects and optimize the use of public resources.Recently, based on fresh frozen tumor samples, our research group has discovered that clear-cellkidney tumors can be classified into four molecular subgroups. Two subgroups are highly sensitiveto the blood vessel inhibitor sunitinib, two other subgroups are less or not sensitive. We now aimto strengthen this model in order to understand better clear-cell kidney tumors and to improvepatient outcome. (A) We will validate our classification on paraphin embedded samples, which aremore largely available than fresh frozen samples. (B) We will deepen the molecularcharacterization of the subtypes through the analysis of micro-RNAs and mutations, and study thestability of this classification throughout disease evolution. (C) We will study the impact of theclassification on patients treated with other blood vessel inhibitors such as pazopanib and axitinib, with mTOR-inhibitors, with new generation immunotherapy and with surgical resection ofmetastases." "RESPONSE PREDICTION IN METASTATIC RENAL CELL CARCINOMA TREATED WITH ANTI-VASCULAR ENDOTHELIAL GROWTH FACTORTARGETED THERAPY AND/OR IMMUNE CHECKPOINT INHIBITORS" "Benoit Beuselinck" "Laboratory of Experimental Oncology" "During the last decade, two active therapeutic approaches have been developed for metastatic kidney cancer: angiogenesis inhibitors and immune checkpoint inhibitors. Both therapies can lead to prolonged disease control. In some cases, immune therapy can even lead to complete remissions. However, not all the patients will respond to one or the other therapy and in many cases, even after a first period of response, the disease will relapse. The underlying mechanisms of efficacy and resistance to these therapies are unknown.As a consequence, there is a high need to develop biomarkers that can predict the efficacy of these therapies in individual patients. Once these biomarkers will be available, it will be possible to choose the right therapy for the right patient, to avoid side effects and possibly reduce the financial burden for the health care system.Moreover, in some  years, patients will probably be treated with combinations of angiogenesis inhibitors and immune therapy, which will lead to improved outcomes, but also to more costs and more adverse events. We will have to identify in advance the patients who will not benefit from any of the compounds, the patients that will only need one of the compounds, and the patients who will need the combination.Therefore, the aim of our research project is to study the mechanisms of resistance to angiogenesis inhibitors and immune therapy in kidney cancer through an in depth study of the tumors and metastases. " "RESPONSE PREDICTION IN METASTATIC RENAL CELL CARCINOMA TREATED WITH ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR TARGETED THERAPY AND/OR IMMUNE CHECKPOINT INHIBITORS" "Benoit Beuselinck" "Laboratory of Experimental Oncology" "In recent years, major improvements have been achieved in the treatment of metastatic clear-cell renal cell carcinoma with the introduction of angiogenesis-inhibitors and immune therapy. Despite highly variable patient responses, no markers for patient treatment selection have entered the clinic thus far. We aim to search for predictive biomarkers in order to select the right patient for the right therapy. This will allow us to obtain better treatment results, to save adverse events in patients in whom the therapy would not work and to use in a more efficient way public finances. We will search for biomarkers through an extensive study of the molecular characteristics of primary kidney tumors and their metastases and genetic characteristics of the patient. We aim to offer an easy way to classify paraffin embedded kidney tumors into our molecular ccrcc1-4 classification, that has a proven prognostic and predictive impact in different therapeutic situations." "Response prediction in metastatic clear-cell renal cell carcinoma treated with angiogenesis and/or immune checkpoint inhibitors" "Benoit Beuselinck" "Laboratory of Experimental Oncology, Urogenital, Abdominal and Plastic Surgery, Laboratory of Cell Stress & Immunity" "Angiogenesis inhibitors (VEGFR-TKIs) and immune checkpoint inhibitors (ICPIs) are efficient therapies for metastatic clear-cell renal cell carcinoma (ccRCC). From 2020 on, standard first-line therapy will be the combination of two ICPIs (nivolumab/ipilimumab) or the combination of one ICPI (pembrolizumab or avelumab) and one VEGFR-TKI (axitinib). VEGFR-TKIs in monotherapy (cabozantinb, axitinib) are used from second-line on. However, few predictive biomarkers are available. Sarcomatoid tumors respond better on ICPIs than on VEGFR-TKIs. VEGFR-TKIs work better in hypervascular and indolent tumors than in tumors with few neoangiogenesis and aggressive tumors. More precise predictive biomarkers would allow a more efficient use of these expensive therapies and to save adverse events in patients in whom these therapies do not work. Our research team has developed a molecular classification of ccRCC with a prognostic and a predictive impact. The aim of this research project is to discover additional predictive biomarkers for ICPIs and for VEGFR-TKIs on top of the molecular classification. We will study (A) HLA-subtypes of the patients suffering ccRCC, (B) mutations in DNA damage repair genes, (C) immune cells and proteins involved in the antitumoral immune reaction and the immune suppressive micro-environment as well as (D) specific characteristics of angiogenesis (such as FGFR2) and mechanisms of resistance to angiogenesis inhibitors (such as cMET)." "Validation of Aprataxin as a biomarker of response to Topoisomerase I inhibitors in cancer patients." "Sabine Tejpar" "Molecular Digestive Oncology" "ERA-Net-E-TRANSCAN research project about the validation of Aprataxin as a biomarker of response to Topoisomerase I inhibitors in cancer patients where we take care of the KRAS mutation analysis and carry out the assessment of Aprataxin immunostainings and participate in the final analysis of the data and in the collection of the sections necessary for the RNA/DNA extraction of the large number of samples." "Targeting the CDA/P2Y6 axis to overcome immunosuppression and favor response to immune checkpoint inhibitors in pancreatic cancer" "Max Mazzone" "Laboratory of Tumor Inflammation and Angiogenesis (VIB-KU Leuven)" "Among the features characterizing the tumor microenvironment (TME), metabolism-mediated immunosuppression is an important factor underlying treatment resistance in pancreatic cancer patients. As such, we will investigate the inhibition of a CDA/UDP/P2Y6 axis in the TME of pancreatic tumors, which we envision holds the potential to improve immunotherapy by breaking tumor-associated macrophage-mediated immunosuppression and sensitizing T cell activation to immune checkpoint blockade." "PRIMMO trial - Extracellular vesicles to predict response to checkpoint inhibitors in cervical and endometrial cancer patients" "Hannelore Denys" "Department of Internal Medicine and Pediatrics" "Onderzoeksbeurs EvdS (Lien Lippens)" "NIPITplus, a multi-cancer blood test to predict immune checkpoint inhibitor response and monitor toxicity" "Katleen De Preter" "Department of Biomolecular Medicine" "The last decade, an increasing number of cancer patients is treated with immune checkpoint inhibitors, however accurate minimal-invasive response prediction tests are lacking. In this project, we will develop the NIPITplus strategy where we perform computational deconvolution and TCR/BCR indexing on bulk sequencing data of blood samples to estimate the proportions of different immune-cell (sub-)types/clones. The deconvolution will be informed by unbiased single-cell RNA profiling of the immune system. Immune cell (sub-)types/clones associated with response will be identified by applying machine learning algorithms. It has been demonstrated that across different cancer entities common immune cell types exist that are predictive for response, therefore, we aim to develop a multi-entity predictor of response by including patients with lung cancer, melanoma and RCC. Finally we will monitor patients and asses the shift in immune cell proportions and TCR/BCR abundances upon occurrence of immune related adverse events during immunotherapy." "Modulating the epigenome using histone deacetylase inhibitors: inducing a type 2 immune response switch to promote recovery after trauma to the spinal cord" "Sven HENDRIX" Morphology "Regeneration and functional recovery after trauma to the adult mammalian central nervous system (CNS) is limited due to extrinsic trauma-induced inflammation and intrinsic low axon growth, among other factors [1]. However, considerable evidence exists, although mostly indirect, that a switch towards a type 2 immune response may contribute to regeneration after CNS trauma [2]. Preliminary data of our group indicate that the anti-inflammatory factors interleukin-4 (IL-4) and IL-13, canonical T helper type 2 (Th2) cytokines, improve neuronal survival and neurite growth in vitro; moreover, in vivo functional recovery of mice with spinal cord injury (SCI) was improved when administering these cytokines as recombinant proteins or secreted by transplanted Th2 cells. A great but yet underexplored potential source for immunomodulation after SCI are histone deacetylation inhibitors (HDACi). It is well-know that Th cell differentiation to Th1 or Th2 can be tightly controlled by HDACi [3]. Furthermore, HDACi have been implicated in the expression of regeneration-associated genes important for axonal regrowth [4]. Therefore, we aim to induce a type 2 immune switch by transplanting Th cells pretreated with HDACi to induce expression of Th2- specific genes, or by direct administration of HDACi, to promote histological and functional outcome in a well-established SCI mouse model. Evaluating the use of HDACi for inducing repair after SCI may lead to new therapeutic approaches in neurotrauma."