24 September 2019
Today, the spiraling prices of immuno-oncology agents threaten the financial sustainability of cancer treatment. This 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. To add insult to injury, the efficacy of immune therapies against various types of cancer is highly variable.In this Grand Challenge project, the aim is to discover why immunotherapy is effective in some patients or in specific cancer types, but not in others. Building on this knowledge, biomarkers will be identified that predict response to Immune Checkpoint Blockade (ICBs). These biomarkers can then be used to tailor treatments to specific patients and cancer types. 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.

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 (patientor treatment level) to ICB
- distilling novel biomarkers predictive of response to ICB 

In the long run, these insights are expected to enable the design of novel treatment combinations that provide long-term therapeutic responses in refractory patients. With this 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 at single cell level. From these studies novel predictive biomarkers will be distilled, and ultimately novel effective combination regimens will be proposed.​

Marlies Vanden Bempt (VIB-KU Leuven Center for Cancer Biology): “As early career researcher, the Grand Challenges projects present a unique opportunity to have a direct impact on society and healthcare.”

The POINTILLISM project involves a multidisciplinary collaboration of the VIB-KU Leuven Center for Cancer
Biology (supervised by Diether Lambrechts and Jean- Christophe Marine) with skilled teams from the
KU Leuven as well as multiple oncologists working under the umbrella of the Leuven Cancer Institute (LKI).
The VIB-KU Leuven Center for Cancer Biology has a unique expertise in studying the tumor microenvironment (TME) and a strong expertise in single-cell profiling techniques and bioinformatics
analyses of single-cell data. The Lab of Thierry Voet (KU Leuven) has world-wide recognized expertise in single-cell omics. The Leuven Single-Cell Center (VIB, KU Leuven) spearheaded the initiation of the Single-Cell Analysis Core within the Genomics Core Leuven. The Leuven Cancer Institute aims to unite all activities
related to cancer care and research within UZ Leuven and KU Leuven. Within Belgium it represents the largest
referral center for cancer patients (34,000 cancer patients in 2017). LKI physicians initiate on average 200 clinical trials per year.

Societal impact
The societal aspect of the project is an extra motivation for the researchers. Some of the most innovative
technologies, more specifically multi-omics single-cell profiling, will be 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 during disease progression.

As such, the single-cell approach is unique, and it is expected to yield extremely rich and fine-grained data
at the highest resolution possible. These data, including biomaterials collected during the project, will be collated into an extensive databank to facilitate future research

Go back to the overview: 'the Grand Challenges Program'​