<i>Porphyromonas gingivalis</i> Promotes Oral Squamous Cell Carcinoma Progression in an Immune Microenvironment

Abstract

Increasing evidence has revealed a significant association between microorganisms and oral squamous cell carcinoma (OSCC). <i>Porphyromonas gingivalis</i>, the keystone pathogen in chronic periodontitis, is considered an important potential etiologic agent of OSCC, but the underlying immune mechanisms through which <i>P. gingivalis</i> mediates tumor progression of the oral cancer remain poorly understood. Our cohort study showed that the localization of <i>P. gingivalis</i> in tumor tissues was related to poor survival of patients with OSCC. Moreover, <i>P. gingivalis</i> infection increased oral lesion multiplicity and size and promoted tumor progression in a 4-nitroquinoline-1 oxide (4NQO)-induced carcinogenesis mouse model by invading the oral lesions. In addition, CD11b⁺ myeloid cells and myeloid-derived suppressor cells (MDSCs) showed increased infiltration of oral lesions. Furthermore, in vitro observations showed that MDSCs accumulated when human-derived dysplastic oral keratinocytes (DOKs) were exposed to <i>P. gingivalis</i>, and CXCL2, CCL2, interleukin (IL)-6, and IL-8 may be potential candidate genes that facilitate the recruitment of MDSCs. Taken together, our findings suggest that <i>P. gingivalis</i> promotes tumor progression by generating a cancer-promoting microenvironment, indicating a close relationship among <i>P. gingivalis</i>, tumor progression of the oral cancer, and immune responses.