Mass cytometry analysis of the tumour-immune landscape: The role of Axl receptor kinase

Abstract

Cancer is one of the leading causes of death in Norway (2016) and worldwide. Despite the advent of new immunotherapies, malignant cancer demonstrates an intrinsic plasticity and is able to evade, adapt and suppress the immune system. An important driver for this malignant phenotype is the epithelial-to-mesenchymal transition (EMT) program, characteristic of stem cells. Previous research showed a link between the AXL receptor tyrosine kinase (Axl) and EMT. The Axl receptor is further involved in immune suppression and could therefore serve as a potential target in immunotherapy and in combination with other cancer treatments. Chemotherapeutic treatment also shows evidence of immune involvement, and the immune system plays a vital role in all forms of cancer treatment. In this study, we evaluated current immunotherapy in combination the Axl kinase inhibitor, bemcentinib. Using single cell mass cytometry we conducted 30 parameter mapping of the immune system in an experimental murine tumour model. The data was analysed using dimensionality reduction and unsupervised clustering. By studying how the immune landscape changes during tumour development and immunotherapy treatment, important insightsinto how the immune system responds to tumour development and treatment was measured and a new treatment regime was evaluated.