P. gingivalis Upregulates PD-L1 (B7-H1) on Various Carcinoma Cells

Objectives: Overexpression of the immune-regulatory PD-L1 (B7-H1) receptor on host cells may impair immune response and modifies inflammation. PD-L1 expression has been detected in a multitude of human carcinomas, leading to anergy and apoptosis of activated T cells, and enabling tumor cells to evade host response. Porphyromonas gingivalis (P. gingivalis) is considered as a keystone pathogen in the etiology of periodontitis and expresses various virulence factors.
Methods: In this study, the expression of PD-L1 on 5 different human carcinoma cells lines originating from tongue (SCC-25), prostate (DU-145), breast (COLO-824), lung (A-427) and colon (CL-11) cancer, were analyzed after stimulation with P. gingivalis membrane proteins. After 48h, the cells were harvested, prepared for Western blot (WB) and analyzed using PD-L1 antibody staining. RNA was extracted and gene expression of PD-L1 was quantified by real-time PCR.
Results: WB revealed that SCC-25, DU-145 and COLO-824 cells showed a slight basal expression of PD-L1 protein, in A-427 and CL-11 cells this basal expression did not occur. After stimulation with P. gingivalis membrane proteins, PD-L1 protein was upregulated 8.1±1.3 fold in in SCC-25, 13.4±2.6 fold in DU-145 and 8.9±4.5 fold in COLO-824 cells (p < 0.05) and clearly detectable in the 2 other tumor cells lines. After 24h expression of PD-L1 mRNA in relation to non-infected cells increased 10.3±2.0 fold in SCC-25, 4.2 ±0.5 fold in DU 145, 7.7±0.2 fold in COLO 824, 1.9±0.03 fold in A427 and 2.1±1.4 fold in CL-11 cells (p < 0.05).
Conclusions: The membrane fraction of P. gingivalis induces the expression of the PD-L1 ligand in tumor cell lines of various origins. Thus P. gingivalis proteins might exhibit immunosuppressive effects in different sites of the body, which might constitute a general mechanism of tumor cells to evade host immune response.