Title: Cancer and viral infections in the lung - a delicate balance of microenvironments
Funder: Cancer Research UK

Abstract: Background: Cancer growth in the lung originating from a primary tumour or from metastatic spread is amongst the most common causes of cancer related mortality. Cancer exists in an environment composed by a pleura of tissue derived non-cancer cells where a fine-tuned equilibrium with immune cells is established. In a specific microenvironment immune cells can either support or thwart cancer growth. The local lung microenvironment is therefore crucial to allow or prevent cancer growth and is shaped by many factors, including inflammation. Lung viral infections elicit inflammation and events such as influenza virus infections in cancer patients have the potential to dramatically perturb the equilibrium between cancer and immune and tissue cells. How lung viral infection influences lung cancer or lung metastatic initiation and progression is not clear. Conversely, it is also apparent that cancer patients show important changes in their immune responses but to what extent cancer development impacts antiviral immunity, including to respiratory viruses, has not been investigated. Aims: We will investigate how acute lung viral infections impact chemically-induced lung carcinogenesis and metastatic spread of cancer to the lung. We will also investigate if respiratory tract infections create an opportunity for a better response to therapeutic interventions and particularly to immune-checkpoints blocker treatments. In addition, we address how the immune response to lung infection is influenced by the presence of a distant tumour such as breast cancer. Methods: We will use well established mouse infection models of respiratory syncytial virus (RSV) and influenza virus in combination with chemically induced lung cancer or lung metastatic mammary tumour models. How the results of this research will be used: These models (cancer/infection) will provide opportunities for mechanistic dissection of the impact of virus-induced immune responses on lung cancers and metastatic spread and vice-versa. This project will be important for enhancing our understanding of how to manage respiratory infections in cancer patients and also, importantly, to assess how respiratory viral infections impact progression of cancer in the lung.

Lay abstract: Background: Cancer growth in the lung originating from a primary tumour or from metastatic spread is amongst the most common causes of cancer related mortality. Cancer exists in an environment composed by a pleura of tissue derived non-cancer cells where a fine-tuned equilibrium with immune cells is established. In a specific microenvironment immune cells can either support or thwart cancer growth. The local lung microenvironment is therefore crucial to allow or prevent cancer growth and is shaped by many factors, including inflammation. Lung viral infections elicit inflammation and events such as influenza virus infections in cancer patients have the potential to dramatically perturb the equilibrium between cancer and immune and tissue cells. How lung viral infection influences lung cancer or lung metastatic initiation and progression is not clear. Conversely, it is also apparent that cancer patients show important changes in their immune responses but to what extent cancer development impacts antiviral immunity, including to respiratory viruses, has not been investigated. Aims: We will investigate how acute lung viral infections impact chemically-induced lung carcinogenesis and metastatic spread of cancer to the lung. We will also investigate if respiratory tract infections create an opportunity for a better response to therapeutic interventions and particularly to immune-checkpoints blocker treatments. In addition, we address how the immune response to lung infection is influenced by the presence of a distant tumour such as breast cancer. Methods: We will use well established mouse infection models of respiratory syncytial virus (RSV) and influenza virus in combination with chemically induced lung cancer or lung metastatic mammary tumour models. How the results of this research will be used: These models (cancer/infection) will provide opportunities for mechanistic dissection of the impact of virus-induced immune responses on lung cancers and metastatic spread and vice-versa. This project will be important for enhancing our understanding of how to manage respiratory infections in cancer patients and also, importantly, to assess how respiratory viral infections impact progression of cancer in the lung.

Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS;2.2 FACTORS RELATING TO PHYSICAL ENVIRONMENT
Health categories: CANCER AND NEOPLASMS