Copd-肺がん合併症の病態メカニズム解明

Abstract

Chronic obstructive pulmonary disease (COPD) is the third leading cause of death in the world and is characterized by inflammation, emphysema and respiratory dysfunction. The development of radical treatment and the achievement of long-term disease management are urgent issues for COPD. Because COPD is highly complicated with lung cancer and this complication leads to poor prognosis, it is very important to elucidate its pathological mechanism and develop a novel therapeutic strategy. Previous research showed the relationship between lung cancer and COPD-derived inflammation, but not emphysema. Therefore, I selected elastase model and induced lung cancer using tobaccospecific carcinogenesis (NNK) for lung cancer initiation stage model (COPD-NNK) and lewis lung carcinoma (LLC) for lung cancer exacerbation stage (COPD-LLC). In COPD-NNK model, incidence of lung tumors was increased but COPD phenotypes were not exacerbated. Moreover, I found that α7nAChR-p-Akt pathway was activated in these tumors. Additionally, the survival rate was decreased and intratumor T cells and immune checkpoint protein PD-L1positive macrophages were increased in COPD-LLC model. In contrast, the survival rate was increased in anti-PD-L1 antibody-treated COPD-LLC model. These results suggested that PD-L1-positive macrophages inhibited T cell activity and decreased the survival rate. In this study, I revealed changes in tumor microenvironment and exacerbation mechanism in COPD-lung cancer complication.