While recent research has improved treatment of primary tumours, few discoveries have specifically benefited patients with metastatic disease such as brain metastases. The microenvironment is a key component that regulates metastasis colonization; however, little is known about the spatial heterogeneity of the human brain metastatic niche. We will therefore apply spatial single-cell transcriptomic sequencing and multiplex immunohistochemistry (mIHC) to characterize the properties and spatial distribution of tumour and immune cells in brain metastases from melanoma, breast and lung cancer patients. We reason that future therapeutic strategies should target communities of tumour and immune cells and their signalling networks rather than individual genes or cell types.
Using spatial whole transcriptomics on four lung cancer brain metastases we have previously shown that lung cancer brain metastases exhibit significant interpatient heterogeneity in their gene expression but feature consistent immune cell communities that could be clinically exploited. The prognostic and therapeutic implications of these immune and tumour communities are still unknown but will be explored in this project which includes brain metastases from 56 patients.
Contact: Catharina Hagerling catharina.hagerling@med.lu.se