Mid-Term Report Summary - MACTHERVAC (Modulation of a novel population of immune suppressive tumoural macrophages and the therapeutic vaccination of cancer)
Tumour associated macrophages (TAMs) are one of the most abundant stromal cell types in cancer, and promote tumour progression through supporting angiogenesis, immune suppression and tumour cell migration. However, there is increasing evidence to suggest that the functions of these cells could be associated with specific subsets. It has been demonstrated that TAMs expressing the cell surface protein fibroblast activation protein-alpha (FAP) co-express heme oxygenase-1 (HO-1), an inducible enzyme responsible for the breakdown of heme to generate the biologically active molecules biliverdin, ferrous iron and carbon monoxide. FAP+ TAMs expression of HO-1 has been implicated in tumoral immune suppression. We have analysed FAP+ TAMs in the aggressive autochthonous murine model of mammary adenocarcinoma (MMTV-PyMT). We have demonstrated that FAP+ TAMs reside in this model, however pharmacological inhibition of HO-1 does not effect tumour growth as a single agent. We have generated a vaccine to raise an anti-tumour immune response against a tumour associated antigen in this model and will investigate whether the inhibition of HO-1 might potentiate the efficacy of a therapeutic cancer vaccine. We have generated transgenic mouse models to both report and modulate FAP+ TAM function, and have also acquired transcriptomic data from these cells to investigate the proteins and pathways which these utilise to facilitate their function within the tumour microenvironment.
Paul Labbett, (Director Research grants and contracts)
Record Number: 189060 / Last updated on: 2016-09-19