Impact of periodontal microbiome on response to immunotherapy in patients with advanced non-small cell lung cancer (NSCLC).

Abstract

e20549 Background: The correlation between microbiota dysbiosis and cancer has gained extensive attention and has been widely explored. Although previous findings uncovered the critical roles of microbiota in tumorigenesis and response to immunotherapy, most of them were focused on the intestinal microbiota rather than oral and lung microbiota. Notably, the considerable functions of microbiota in maintaining lung homeostasis should not be neglected, as microbiome dysbiosis may promote lung cancer evolution and progression. The impact of the microbiome associated with periodontitis on lung cancer patients remains controversial and poorly explored. This study evaluates the effect of microorganisms associated with periodontitis on levels of PD-L1 expression, response to first—and second-line therapy, and progression-free survival (PFS) in patients with advanced NSCLC treated with ICIs +/- chemotherapy. Methods: Twenty-two individuals were included. Saliva and buccal swabs were obtained and processed using qPCR techniques to determine the presence and concentration of culturable and non-culturable target periodontopathic microorganisms. The frequency and concentration of microorganisms were correlated with response rate (ORR) and PFS. Results: Microbiological results revealed differences in periodontopathic microorganisms in saliva samples of NSCLC patients with a significant increase in Treponema denticola (p=0.018), Tanerella forsythia (p=0.022), Eubacterium brachy (p=0.014), Filifactor alocis (p=0.014), and Eubacterium nodatum (p=0.021). Significant differences were also observed in ORR according to increased levels of Tanerella forsythia (p=0.02), Eubacterium brachy (p=0.040), Eubacterium nodatum (p=0.019) and Fusobacterium nucleatum (p=0.05). A higher concentration of Filifactor alocis (p=0.001) was associated with a lower PFS to first-line treatment with ICIs +/- chemotherapy. Patients with altered concentrations of these microorganisms showed low levels of PD-L1 expression in tumor tissue (p<0.05). Conclusions: Periodontopathic bacteria have different concentrations in patients with NSCLC, and their variation affects the outcomes of immunotherapy treatment. Future studies should explore the influence of these microorganisms on the immune-mediated response, resistance to immunotherapy, and various interventions that allow normalizing oral dysbiosis.