Ontogeny and function of tumour-associated macrophages
Speaker: Toby Lawrence
Institution: Centre for Inflammation Biology and Cancer Immunology, King’s College London. London, United Kingdom
There is now a wealth of clinical and experimental evidence that strongly links the accumulation of tumour-associated macrophages (TAM) with cancer progression, invasion and metastasis. In the vast majority of published studies increased numbers of TAM correlate with poor prognosis, but in some cases, specific TAM subsets have been associated with beneficial outcomes – which may reflect their roles in orchestrating protective immune responses. In fact, recent studies using paired single cell analysis by mass cytometry and RNA sequencing, have revealed an unprecedented level of diversity among TAM in human cancer. But will still understand little about the significance of TAM heterogeneity and the functions of different TAM subsets in disease progression, which is critical to design more targeted therapies.
We have characterised the ontogeny and function of different TAM subsets in experimental models of cancer. We have demonstrated that a subset of monocyte-derived macrophages (MDM) that express the scavenger receptor CD163, exert profound immune-suppressive functions and prevent the mobilisation of anti-tumour immune responses. In other studies, we have characterised subsets of tissue-resident macrophages of embryonic origins (TRM), which specifically promote the invasive activity of disseminated cancer cells and the metastatic spread of disease. Our studies suggest monocyte-derived and tissue-resident TAM subsets have divergent functions in tumour progression and we are actively exploring the molecular basis of TAM diversity.