The presence of intratumoral Porphyromonas gingivalis correlates with a previously defined pancreatic adenocarcinoma, immune cell expression phenotype and with tumor resident, adaptive immune receptor features

Author:

Kinskey Jacob C1,Huda Taha I2,Gozlan Etienne C2,Quach Jessica U2,Arturo Juan F2,Chobrutskiy Andrea3,Chobrutskiy Boris I4,Blanck George25ORCID

Affiliation:

1. Department of Pathology and Genomic Medicine, Houston Methodist Hospital , Houston, TX 77030 , USA

2. Department of Molecular Medicine, Morsani College of Medicine, University of South Florida , Tampa, FL 33612 , USA

3. Department of Pediatrics, Oregon Health and Science University , Portland, OR 97239 , USA

4. Department of Internal Medicine, Oregon Health and Science University , Portland, OR 97239 , USA

5. Department of Immunology, H. Lee Moffitt Cancer Center and Research Institute , Tampa, FL 33612 , USA

Abstract

Abstract The association between pancreatic adenocarcinoma (PAAD) and the pancreatic microbiome is not fully understood, although bacteria may decrease the effectiveness of chemotherapy and lead to anti-apoptotic, pro-inflammatory microenvironments. To better understand the relationship between the PAAD microbiome and the microenvironment, we identified Porphyromonas gingivalis-positive PAAD samples and found a strong association between intratumoral P. gingivalis and: (i) an immune cell gene expression phenotype previously defined by others as gene program 7; and (ii) recovery of immunoglobulin recombination, sequencing reads. We applied a novel chemical complementarity scoring algorithm, suitable for a big data setting, and determined that the previously established P. gingivalis antigen, rpgB had a reduced chemical complementarity with T-cell receptor (TCR) complementarity-determining region-3 amino acid sequences recovered from PAAD samples with P. gingivalis in comparison to TCR-rpgB chemical complementarity represented by the PAAD samples that lacked P. gingivalis. This finding strengthens the existing body of evidence correlating P. gingivalis with PAAD, which may have implications for the treatment and prognosis of patients. Furthermore, demonstrating the correlation of P. gingivalis and gene program 7 raises the question of whether P. gingivalis infection is responsible for the gene program 7 subdivision of PAAD?

Publisher

Oxford University Press (OUP)

Subject

Cancer Research,General Medicine

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