Cancer Immunology:

Hedgehog signalling in the Immune System

Hedgehog is an ancient cell-cell signal transduction pathway known to control embryonic development and adult tissue maintenance. In vertebrates the pathway is tied to the primary cilium – a hairlike signalling organelle protruding from nearly every cell in the body.

The cells of the immune system do not form primary cilia. Instead, they form immune synapses, that are morphologically very similar to the primary cilium, to communicate with each other and the environment.

We have previously shown that Hedgehog is activated downstream of the T cell receptor at the immune synapse of CD8 T cells and controls killing in vitro. We now want to understand how the diverse cells of the immune system differentially exploit Hedgehog signalling in vivo in the context of cancer, infection, and autoimmunity.

The laboratory has generated unique mouse models and reagents to investigate the role of Hedgehog signalling in various immune cell subsets and is running a clinical trial investigating the role of Hh-mutations and Hedgehog inhibitor treatment in cancer patients.

We aim to characterise the distinctive mechanistic features of immune Hedgehog signalling with the long-term goal to modulate Hh signalling in immune cells to improve immune responses in the context of cancer, infection, autoimmunity and vaccination.

Actin rearrangement and centrosome polarisation in CD8 T cells on contact with a tumour cell

scRNAseq analysis of CD3+ single positive thymocytes (CD4+ or CD8+) showing immature (CD24+) and mature (CD62L+) populations allowing us to investigate thymocyte maturation in the absence of Gli1.

HiPlex RNAscope analysis of thymic sections showing expression of Hedgehog pathway ligands within the cortex and medulla regions. HALO software allows analysis, localisation and quantification of up to 12 multiplexed fluorescent RNAscope probes.

Tumour-infiltrating immune subsets with 8-panel immunofluorescence in Basal Cell Carcinoma patient biopsies and corresponding H&E staining. Scale bar=100μm.