Long-lasting alterations in lung anti-tumor immunity by viral infections

Abstract

Respiratory viruses are widespread human pathogens capable of inducing profound and long-lasting changes in our immune system. In this context, we hypothesized that the individual history of respiratory viral infections could shape the lung microenvironment and could affect anti-tumor immunity, thus influencing the establishment and progression of lung tumors. To investigate this question, two different viruses were used in this study: Murid herpesvirus 4 (MuHV-4), and Pneumonia virus of mice (PVM), respectively homologs of widely distributed human viruses, Epstein-Barr virus (EBV) and Respiratory Syncytial Virus (RSV). In our experimental setting, we implanted tumors in mice one month after infection. We used Lewis lung carcinoma (LLC) cells and followed two models of tumor development: orthotopic, in which LLC cells were inoculated intratracheally directly into the lung, and metastasis, in which LLC cells were injected intravenously. One month after infection, two types of murine models of Lewis lung carcinoma (LLC), an orthotopic model or a metastasis model, were inoculated intratracheally or intravenously respectively. The results revealed that MuHV-4 and PVM infections affect lung tumor development in opposite ways. MuHV-4 pre-infection reduced tumor establishment, while PVM pre-infection promoted early tumor establishment and boosted tumor growth. MuHV-4 infection stimulated a strong memory T cell response, potentially responsible for the protective effect against tumors. In contrast, PVM infection led to defective T cell responses and enhanced inflammation, that may contribute to a pro-tumoral phenotype. Thus, certain common respiratory viruses known for their oncogenic potential, seem also to be able to confer protection in a context-dependent manner, while others, responsible for a transient infection can have a deleterious long-term impact on the immunity of the lung. Therefore, the individual history of viral infections can shape the lung microenvironment and modulate individual susceptibility to the development of lung tumors. Understanding these complex interactions between viruses, the immune system, and the tumor microenvironment can offer valuable insights for future research and potential therapeutic strategies.