171P an Unwelcome Guest: P. Gingivalis Intratumoral Infection and Immune Evasion in Gastric Cancer

Periodontal disease (PD) is an inflammatory condition that affects oral tissue, resulting from dysbiosis and maintaining a low systemic inflammatory response. P. gingivalis is a flagship bacterium in oral dysbiosis and periodontal disease. Previous studies have linked PD with a higher risk of gastric cancer (GC). The systemic inflammatory state sustained by PD also causes an immunosuppressive condition led by the activation of immune checkpoints, provoking T cell exhaustion and cancer progression. One of the most fundamental immune pathways in GC is the PD1/PDL1 activation, as the inhibition of this pathway is currently a standard of care treatment. We explore the relationship between P. gingivalis infection and GC, scrutinizing the immune landscape of these tumors in a cohort of Chilean GC patients. A total of 91 GC patients were included in our observational cohort study. Clinical data were obtained from available medical records. PDL1, HER2, E-Cadherin, P53, P16, MLH1, MSH2, MSH6, PMS2, P. gingivalis LPS (LPS-Pg) were tested by immunohistochemistry in a tissue microarray (TMA). EBV status was confirmed by CISH. Antibodies against cytokeratin, PDL1, PD1, CD8, CD45. CD3 and CD68 were tested in two panels. All patients signed informed consent to participate in the study. The prevalence of P. gingivalis intratumoral infection detected by LPS-Pg presence on GC patients is 19.8%. These LPS-Pg (+) patients have significantly less locally advanced disease. Moreover, we found a statistical difference in EBV status where EBV+ cases were 9.6% in LPS-Pg (-) and 27.8% in LPS-Pg (+) (p=0.041). Cell counts positive to PD1 and PDL1 were statistically different between LPS-Pg (+) and LPS-Pg (-) patients. Survival analysis by Kaplan-Meier estimates adjusted by GC staging at diagnosis showed differences in median overall survival, 49 months in LPS-Pg (-) and 17 months in LPS-Pg (+) (p<0.05). LPS-Pg infection upregulates immune checkpoint pathways, potentiating the immune evasion of GC. PD control strategies in these patients could be further evaluated as beneficial when attempting to limit disease progression. Finally, identifying specific changes in oral microbiota and GC progression could lead to future interventional studies.