Oral Presentation 31st Lorne Cancer Conference 2019

Molecular Mechanisms of Growth Factor Surveillance (#19)

Alexander D Barrow 1
  1. University of Melbourne, Melbourne, VIC, Australia

The Barrow lab is interested in a new avenue of immunological research termed ‘growth factor (GF) surveillance’. GFs are over-expressed by tumours to promote angiogenesis, stromal reaction and tumour growth and GF receptor signalling is often dysregulated in cancer cells. By screening a secretome library, we found that the human immunoreceptor NKp44, encoded by NCR2 and expressed on natural killer (NK) cells and innate lymphoid cells (ILCs), recognises platelet-derived growth factor (PDGF)-DD. PDGF-DD engagement of NKp44 triggered NK cell secretion of interferon gamma (IFN)-γ and tumour necrosis factor (TNF)-α that induced tumour cell growth arrest. A distinctive transcriptional signature of PDGF-DD-induced cytokines and the downregulation of tumour cell-cycle genes correlated with NCR2 expression and greater survival in glioblastoma. NKp44 expression in mouse NK cells controlled the dissemination of tumours expressing PDGF-DD more effectively than control mice. Moreover, many viruses encode GFs, which induce proliferative lesions that enhance viral infectivity in vivo and can even promote cellular transformation. We now show that PDGF-DD binding to NKp44 enhances the secretion of type-I interferon from plasmacytoid dendritic cells (pDCs). Given the importance of cellular proliferation and differentiation to the life cycle of many different tumours and pathogens, we predict GF surveillance could be more broadly employed by the immune system and evolved to combat the threat of infectious disease as well as cellular transformation.