Pointillism: improving immune checkpoint inhibitor response by single-cell integrative multi-omics of the tumor ecosystems


In this Grand Challenge, the aim is to discover why immunotherapy is effective in some patients or
in specific cancer types, but not in others. From this knowledge, biomarkers will be identified that
predict response to Immune checkpoint inhibitors (ICBs). 
Furthermore, the cellular and molecular mechanisms by which immune and cancer cells interact will be further unraveled to ultimately guide the clinical implementation of more effective and truly transformative cancer immune-oncology treatment combinations.

Today the spiralling prices of immuno-oncology agents threaten the financial sustainability of cancer treatment and the situation has only worsened since it became clear that these drugs need to be combined for optimal clinical results. With a lifetime risk of developing cancer of close to 40%, the disastrous financial impact on society is clear.
In this Grand Challenge, 4 immunotherapy trials will be initiated which involve anti-PD1/PDL1 compounds in indications of unmet clinical need. A comprehensive and unique collection of pre- and on-treatment biopsies from all patients will be assembled. These samples will be used to establish dynamic maps of the entire tumor ecosystem before and during ICB using innovative and integrative single-cell profiling methods. 
On the short term, this will allow:
  • ​monitoring of therapeutic response at unprecedented resolution, 
  • acquisition of information on resistance (patient- or treatment level) to ICB
  • distilling novel biomarkers predictive of response to ICB
In the long run, these insights are expected to enable revealing of novel treatment combinations that provide long-term therapeutic responses in refractory patients.


In this Grand Challenge, the most innovative technologies, more specifically multi-omics single-cell profiling, are used for the first time in the context of clinical trials, as opposed to the ‘classical’ approach to apply omics analysis on tumor bulk. Specifically, tumor biopsies will be collected in patients receiving ICB before and during treatment, as well as at disease progression. As such, the single-cell approach is unique, and will yield extremely rich and fine-grained data at the lowest resolution possible.
With this VIB-GCP project, the understanding of the molecular and cellular mechanisms underlying resistance to ICB will be unraveled by establishing dynamic (spatial) maps of the tumor ecosystem exposed to ICB. From these studies novel predictive biomarkers will be distilled, and ultimately novel effective combination regimens will be proposed.

 

 Pointillism: predicting cancer immunotherapy response

 
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Participants

VIB-GCP POINTILLISM, involves a multidisciplinary collaboration of the VIB Center for Cancer Biology (VIB-CCB) with skilled teams from the University of Leuven (KULeuven), as well as multiple oncologists working under the umbrella of the Leuven Cancer Institute (LKI). 

CCB has a particularly unique expertise in studying the tumor microenvironment (TME) and several CCB groups have recently developed a strong expertise in single-cell profiling techniques and
bioinformatics analyses of single-cell data. The Laboratory of Thierry Voet (KULeuven) has world-wide recognised expertise in single-cell omics and in addition the Leuven Single-cell Center (VIB, KULeuven) spearheaded the Single Cell Analysis Core within the Genomics Core Leuven. LKI aims at uniting all activities related to cancer care and research within the University Hospitals Leuven (UZLeuven) and KULeuven. LKI groups general and organ system-oriented oncologists and researchers and within Belgium and represents the largest referral center for cancer patients (34.000 cancer patients in 2017). LKI physicians on average initiate ~200 clinical trials per year.

VIB-KU Leuven
KU Leuven 
  • Thierry Voet
KU Leuven-UZ Leuven 
  • Ignace Vergote
  • Sabine Tejpar
  • Hans Wildiers
  • Paul Clement
  • Olivier Bechter
  • Michel Bila
  • Ann Smeets
-> Go back to the overview page of ​ 'VIB Grand Challenges Program'​
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 Prof. Jean-Christophe Marine​​       Prof. Diether Lambrechts   ​