Role of intestinal metabolites in the impact of obstructive sleep apnea on immunotherapy for lung cancer

<bold>Background:</bold> Administration of immune checkpoint inhibitors(ICIs) improves prognosis of lung cancer patients, but its response rate is limited. Recently, reports that obstructive sleep apnea(OSA) causes immune disorders and gut microbiota dysbiosis suggest that OSA may impair the prognosis of lung cancer patients receiving ICIs. <bold>Methods:</bold> In this prospective cohort study, we enrolled lung cancer patients who planned to use first-line ICIs. All patients underwent sleep monitoring and collected blood and fecal samples at baseline. The primary endpoint was progression-free survival(PFS). <bold>Results:</bold> A total of 115 patients were enrolled, of which 60 were tested for gut microecology and further analyzed. Median PFS was significantly decreased in lung cancer patients with OSA compared to those without OSA(3.0mo[1.3-4.7] vs. 6.0mo[5.2-6.8], p=0.001). Fecal s-adenosylhomocysteine(SAH) was significantly decreased in lung cancer patients with OSA, and a decrease in SAH corresponded to a significant reduction in PFS. SAH level was negatively associated with the abundance of microbiota that was harmful to ICI efficacy. SAH level was related to a decrease in peripheral CD3+T cells and class-switched memory B cells, as well as an increase in Treg cells. These immune alterations corresponded to better prognosis. <bold>Conclusion:</bold> OSA impairs the prognosis of lung cancer patients receiving first-line ICIs, and SAH may be the core link. <fig><object-id>erj;64/suppl_68/PA5334/F1</object-id><object-id>F1</object-id><object-id>F1</object-id><graphic></graphic></fig>