M.globosa promotes lung cancer progression and M2 macrophage polarization through oxidative phosphorylation

The lungs are colonized by a variety of microbes which play a significant role in lung cancer progression. In this study, we conducted an in-depth analysis of metagenomic sequencing data obtained from alveolar lavage fluid (ALF) samples of patients with non-small-cell lung cancer (NSCLC) at different clinical stages. The nested qPCR was used to validate the abundance of key fungi and establish a correlation between fungi abundance and patient prognosis. We found that elevated levels of M.globosa correlated with patients at stage1B-3 and worse prognosis. M.globosa enhanced the proliferation of lung cancer cells and promoted tumor growth in vivo by promoting M2-like macrophage polarization, which was primarily driven by oxidative phosphorylation (OXPHOS) activation. The inhibition of OXPHOS in tumor-bearing mice using metformin significantly retarded the tumor growth induced by M. globosa. Together, our clinical observations and experimental findings suggest that intracellular M. globosa infection may contribute to lung cancer progression through immunometabolic remodeling of macrophages.