The role of alternatively-activated macrophages in the development of a lung pre-metastatic niche

Cancer is a leading cause of death worldwide; with the introduction of novel therapies it has become clear that the immune system can be harnessed to fight cancer. We now know that the immune system is an essential component of all tumours and that the inflammatory microenvironment is important in dictating tumour development. Type-2 immune cells, like the ones seen in asthmatic patients, often promote tumorigenesis. Although, epidemiological analyses have also supported associations between IgE-levels with lower risks of cancer. From a clinical perspective, metastasis is the most critical aspect of tumorigenesis, causing over 90% of cancer related deaths. Therefore, understanding how type 2 immune cells in the lung help to create an environment that allows for the engraftment of metastasis would greatly benefit patients. Preliminary data have indicated an important role for alternatively-activated macrophages in this process. Within this proposal I hypothesize that persistent type-2 inflammation in the lung creates a local pre-metastatic environment, possibly by changing the macrophage phenotype, that allows for tumour cell growth and metastatic development. Understanding the molecular pathways and cell types that contribute to the development of a metastatic niche will contribute to the development of novel treatments and biologicals for patients with metastatic disease.