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.

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?

High Level Immunoglobulin Gene Expression and Reduced Intra-tumoral Bacteria Associated With the Transition from Initial to Progressive Diffuse Intrinsic Pontine Glioma.

BACKGROUND/AIM: In the past decade, diffuse intrinsic pontine glioma (DIPG), the most common childhood brainstem glioma, has benefitted from an increase in tissue-based research because of improved biopsy collection techniques. However, the adaptive immune receptor (IR) features represented by tumor material and tumor infiltrating lymphocytes have remained poorly understood. MATERIALS AND METHODS: Herein, we characterized the adaptive immune parameters of DIPG through the recovery of IR recombination reads from RNAseq files representing initial and progressive DIPG samples. RESULTS: An elevated level of immunoglobulin gene expression in the progressive DIPG sample files and a reduced number of bacterial sequencing read recoveries in comparison to RNAseq files representing the initial form of DIPG, was found. Furthermore, the RNAseq files representing both initial and progressive DIPG samples had significant numbers of reads representing Cutibacterium acnes, a bacterium previously linked to prostate cancer development. Results also indicated an opportunity to distinguish overall survival probabilities based on IGL complementarity determining region-3 amino acid sequence physicochemical parameters. CONCLUSION: Genomics analyses allow for a better understanding of adaptive IR features and bacterial infections in the DIPG setting.

Specific Intratumor Bacteria Genera and TRG Recombinations Associated with Greater Survival Probability in Alimentary Tract Cancers.

INTRODUCTION: There remains a lack of knowledge regarding the effects of the intratumor microbiome on the tumor immune milieu. We aimed to investigate whether intratumoral bacterial RNA sequence abundance in gastric and esophageal cancers is associated with T-cell infiltrate features. METHODS: We assessed cases representing the stomach adenocarcinoma (STAD) and esophageal cancer (ESCA) databases of The Cancer Genome Atlas. RNA-seq data estimating intratumoral bacterial abundance was obtained from publicly available sources. TCR recombination reads were mined from exome files. Survival models were generated using the lifelines python package. RESULTS: Increasing levels of the Klebsiella genus were associated with a better OS probability (hazard ratio, 0.5), via a Cox proportional hazards model. The higher Klebsiella abundance was associated with a significantly increased overall (p = 0.0001) and disease-specific survival (p = 0.0289) probability for the STAD dataset. Cases representing the upper 50th percentile of Klebsiella abundance also represented a significantly increased recovery of TRG and TRD recombination reads (p = 0.00192). Analogous results were found for the Aquincola genus in ESCA. CONCLUSIONS: This is the first report of associations between low biomass bacterial samples from primary tumor samples with patient survival and with an increased gamma-delta T cell infiltrate. Results indicate that the gamma-delta T cells potentially play a role in the dynamics of the bacterial infiltration of primary tumors of the alimentary tract.

Bacterial Sequencing Reads in Blood Exome Files from Melanoma and Cervical Cancer Patients are Associated with Cancer Recurrence.

Bacteremia poses great risk for morbidity and mortality for immunocompromised cancer patients. Although the presence of bacteria within solid tumors is gaining greater attention, few studies have analyzed species of bacteria in the blood and their effect on cancer clinical outcomes. Using the Kraken 2 taxonomic profiling tool, we classified bacteria present in blood and primary tumors of cervical cancer and melanoma cases. The Cancer Genome Atlas (TCGA) melanoma blood exome files with Pseudomonas species were found to represent a worse disease-free survival (DFS) probability, while a worse overall survival (OS) result was evidenced for both the TCGA and Moffitt Cancer Center melanoma datasets. Cervical cancer cases with reads representing the Bradyrhizobium genus and Bradyrhizobium sp. BTAi1 found in blood and tumor exome files were found to have lower DFS. Additionally, reduced DFS and OS were observed for cervical cancer cases positive for Bacteroides species including Bacteroides fragilis. This study provides novel evidence and a novel approach for indicating that bacteria in blood is associated with cancer recurrence. These findings may guide the development of more efficient prognostic and screening tools related to bacterial blood infections of melanoma and cervical cancer patients.