Grant: CIHR Fellowship

Classical Hodgkin lymphoma (cHL) is a cancer derived from white blood cells and typically occurs in young adults under the age of 30. Despite the fact that most patients can be cured with chemotherapy, 30% still experience relapse and eventually succumb to their disease. There is now increasing evidence that not only tumour cells, but also normal immune cells surrounding them ("tumour microenvironment, TME"), are of importance for tumour development and growth. Cancer cells influence the composition of their TME in many ways, resulting in a disabled immune response. Our project aims to reveal how changes in the genetic material of the tumour cells associate with the spatial arrangement and functional properties of immune cells in the TME. We propose to comprehensively characterize patients' biopsies using two novel technologies from the respective fields of cancer genomics and cancer imaging: Imaging Mass Cytometry (IMC) and single cell sequencing (scRNAseq and scWGS). IMC takes advantage of detecting and visualizing over 40 different protein markers to label cell types at the same time in the spatial context. Single cell genomics uncovers changes in the genetic material of cancer cells on the individual cell level. Our proposed studies will bring to bear, for the first time, single cell sequencing techniques to study cHL - allowing direct measurement of how genomic alterations in the malignant cells of cHL influence the composition and architecture of the TME. Our study will change the current paradigm of biological studies in cHL as we will establish comprehensive and integrative views on how different cell types in the cancer interact and form cellular 'ecosystems'. Our approach and technical solutions will generate new knowledge that will be the foundation for better diagnostic testing. Moreover, it will lead to novel and refined immunotherapies that alter anti-tumour immune responses and result in higher cure rates and less toxic treatments for patients.