Background
Neutrophils are essential immune cells for anti-microbial defence and neutrophil defects leave the host critically immunocompromised. However, recent work has revealed that these leukocytes also play important roles in cancer with both potent anti- and pro-tumour activity. Neutrophils have been found to be potently pro-metastatic in models of colorectal, breast, and most relevant to this project, pancreatic cancer.
Recent work has established that there is a much higher degree of heterogeneity in neutrophil phenotype than was previously appreciated. This plasticity is surprising on one level due to the relatively short life of the cells, but on another level, we now understand both heterogeneity in ontogeny and environment-driven plasticity to be a key feature of other myeloid cells.
Neutrophil heterogeneity can be both regulated at a systemic level and local level, due to changes in neutrophil production (e.g. “emergency granulopoiesis”) and tissue imprinting. Our own work has uncovered features consistent with extramedullary granulopoiesis within liver tumours as well as highlighting the spleen as a relevant extramedullary production site in cancer capable of producing neutrophils distinct from those that originate in the bone marrow.
Research question
This project will build on previous work in our labs and others, and use sophisticated, disease positioned mouse models to interrogate the role of neutrophils produced outside of the bone marrow in pancreatic cancer progression and metastasis.
Skills/techniques that will be gained
The project will use advanced techniques to:
