Single cell profiling of different cancer types before and during immune checkpoint therapy

Cancer immunotherapy using immune checkpoint blockade (ICB) has created a paradigm shift in the treatment of advanced-stage cancers. However, one of the limitations of ICB is that it provides durable clinical responses only in a small fraction of patients. Therefore, there is an urgent need to determine biomarkers that predict response to ICB, since these are currently not available. Furthermore, there is tremendous potential to enhance the clinical benefits of current ICB, by unraveling underlying mechanisms of action, developing novel synergistic therapies and combine them with approved checkpoint inhibitors.

At the VIB Center of Cancer Biology in collaboration with KU Leuven and the University Hospital, a single-cell multi-omics platform is developed for single-cell profiling of tumor tissue derived from cancer patients treated with ICB in the context of the VIB Grand Challenges program ‘Pointillism’. Pre-, post- and on-treatment biopsies are collected from a selection of patients of a variety of tumor types and dynamic maps of the entire tumors are established using innovative and integrative single-cell profiling methods, such as (spatial) single cell transcriptomics combined with CITE-seq (to determine cell surface antigen expression), immune receptor and antigen specificity profiling. On the short term, this will allow to monitor therapeutic response at unprecedented resolution, provide information on mechanisms of sensitivity and resistance to ICB and distill novel biomarkers predictive of response. In the long run, new insights are generated to reveal novel treatment combinations that provide long-term therapeutic responses in refractory patients.

The VIB CCB single-cell multi-omics platform including Pointillism, is founded around a set of core capabilities comprising (i) the know-how and expertise on single-cell technologies, (ii) a pipeline of standardized procedures and (iii) a robust data management system. Crucial to the achievement of the deliverables and the expected outcome of this initiative is the excellent collaboration with the university hospital. Currently applied for the analysis of breast cancer, head & neck squamous cell carcinoma, recurrent cervix carcinoma and metastatic melanoma in a multitude of investigator driven clinical trials, any other cancer type, for which clinical samples of patients treated with ICB are available, can be integrated on demand thereby demonstrating the generic capacity of the initiative.

Authors

Marlies Vanden Bempt (1)
Vincent Van Hoef (1)
Els Hermans (1)
Hanne Vos (2,3)
Michel Bila (4)
Siel Olbrecht (2,5)
Paul Clement (2,6)
Hans Wildiers (2,3,6)
Ann Smeets (2,3,6)
Ignace Vergote (2,5)
Oliver Bechter (2,7)
Sabine Tejpar (2,7)
Sofie Bekaert (8)
Thierry Voet (9,10)
Chris Marine (1)
Diether Lambrechts (1)

Organisations

VIB-KU Leuven Center for Cancer Biology, Leuven, Belgium (1)
Department of Oncology, KU Leuven, Belgium (2)
Multidisciplinary Breast Centre, University Hospitals Leuven, Belgium (3)
Department of Oral and Maxillofacial Surgery, University Hospitals Leuven, Leuven, Belgium (4)
Department of Gynaecology and Obstetrics, University Hospitals Leuven, Belgium (5)
Department of General Medical Oncology, University Hospitals Leuven, Leuven, Belgium (6)
Department of Digestive Oncology, University Hospitals Leuven, Leuven, Belgium (7)
VIB Headquarters, Gent, Belgium (8)
Wellcome Sanger Institute, Wellcome Genome Campus, Cambridge, UK (9)
Laboratory of Reproductive Genomics, Department of Human Genetics, KU Leuven, Leuven, Belgium (10)

Presenting author

Marlies Vanden Bempt, Grand Challenge coordinator, VIB Center for Cancer Biology
marlies.vandenbempt@kuleuven.vib.be
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