Research Timon Vandamme

Abstract

T-cells are not only crucial actors in our defense against microbes but play an important role in protecting us from cancer. T-cells recognize their targets via its T-cell Receptor (TCR), which consists of a TCRa and TCRb chain. It has been shown that the cancer tissue TCR repertoire holds capacity in predicting which cancer patients will respond to checkpoint-inhibitor therapy, thereby supporting the concept that the tissue-specific TCR repertoire may be considered a stratification biomarker. Decoding the paired TCRab repertoire from the routinely obtained FFPE tissue, necessitates the development of a new single cell workflow method that will allow FFPE tissue paired TCRab sequencing. This would potentially represent a revolution, not only in oncology, but in autoimmunity diseases too where rogue Tcells could be found in affected tissues. In this project, we will create, develop and validate an experimental protocol to obtain paired TCRab data from FFPE tissue.

Researcher(s)

• Promoter: Ogunjimi Benson
• Co-promoter: Vandamme Timon

Research team(s)

• Centre for Health Economics Research and Modelling of Infectious Diseases (CHERMID)

Project type(s)

• Research Project

Abstract

Neuroendocrine neoplasms (NENs) require regular assessment of tumor growth and treatment response. However, adequate, non-invasive tumor markers are currently lacking. Recently, we demonstrated that sequential genome-wide copy number alteration (CNA) profiling of circulating cell-free DNA (ccfDNA) could serve as novel, non-invasive biomarker in NEN patients. Expanding upon these findings, we will explore and benchmark a new analytical approach, GIPXplore, against the current gold standard for ccfDNA CNA analysis (ichorCNA). Moreover, aberrant methylation in ccfDNA will be analyzed using the novel, highly sensitive MSRE-smMIP-seq technology. Both methods for detection and quantification of tumoral DNA will be correlated to clinical outcomes in an extensive prospectively collected cohort of 250 NEN patients. This cohort will be established through the international collaboration between the Belgian ENETS CoEs and Dutch FORCE initiative. In doing so, we will validate the potential added value of ccfDNA analysis for clinical decision-making in NEN patients and facilitate clinical implementation.

Researcher(s)

• Promoter: Vandamme Timon

Research team(s)

• Center for Oncological Research (CORE)

Project type(s)

• Research Project

Abstract

Neuroendocrine neoplasms (NENs) exhibit clinical and biological heterogeneity, making diagnosis extremely challenging. Moreover, NENs tend to progress slowly necessitating long-term follow-up to monitor tumor growth and response to therapy. Current modalities for diagnosis and follow-up of NENs are primarily based on imaging and (repeated) tissue biopsies, but these suffer from several shortcomings which has a direct impact on patients' lives. Over the past few years, liquid biopsies have gained interest as a minimallyinvasive way for rapid tumor detection and collection of molecular information of the tumor with circulating tumor DNA (ctDNA) as one of the most promising new markers. This ctDNA is the fraction of cellfree DNA (cfDNA) released by the tumor, that reflects both the genetic and epigenetic alterations of the tumor. Consequently, this project aims to leverage liquid biopsies to improve diagnostic accuracy in NENs and enable real-time monitoring of NEN patients. For this purpose, NEN-specific molecular alterations namely copy number alterations and differentially methylated CpGs will be identified and selected to enable detection and quantification of ctDNA. Since the gold standard detection methods, shallow whole genome sequencing and methylation arrays, respectively, are not capable to detect very low concentrations of ctDNA, two alternative and highly sensitive multiplex assays based on DNA sequencing and photoelectrochemistry, respectively, will be employed.

Researcher(s)

• Promoter: Vandamme Timon
• Fellow: Vandamme Timon

Research team(s)

• Center for Oncological Research (CORE)

Project type(s)

• Research Project