Periodontitis pathogen Porphyromonas gingivalis promotes pancreatic tumorigenesis via neutrophil elastase from tumor-associated neutrophils

Intratumor microbiome shapes the immune system and influences the outcome of various tumors. Porphyromonas gingivalis (P. gingivalis), the keystone periodontal pathogen, is highly epidemically connected with pancreatic cancer (PC). However, its causative role and the underlining mechanism in promoting PC oncogenesis remain unclear. Here, we illustrated the landscape of intratumor microbiome and its bacterial correlation with oral cavity in PC patients, where P. gingivalis presented both in the oral cavity and tumor tissues. When exposed to P. gingivalis, tumor development was accelerated in orthotopic and subcutaneous PC mouse model, and the cancerous pancreas exhibited a neutrophils-dominated proinflammatory tumor microenvironment. Mechanistically, the intratumoral P. gingivalis promoted PC progression via elevating the secretion of neutrophilic chemokines and neutrophil elastase (NE). Collectively, our study disclosed the bacterial link between periodontitis and PC, and revealed a previously unrecognized mechanism of P. gingivalis in PC pathophysiology, hinting at therapeutic implications.