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The case for immune-based approaches in biliary tract carcinoma.

ABSTRACT: Biliary tract cancers (BTC) comprise a group of uncommon malignancies in which the standard therapies are minimally effective and evolve slowly. Like the majority of gastrointestinal cancers, with some notable exceptions, the impact of immune-based approaches has yet to be seen. However, the etiological background of BTC-overlapping in almost every known causative or associated factor with inflammation-provides a strong clue that these approaches may have an impact in this group of diseases. This review covers what we currently know about the role of the immune system in the etiology of BTC, highlighting differences by subtype, and pointing to the therapeutic opportunities currently entering the clinic or about to do so. (Hepatology 2016;64:1785-1791).

SUBMITTER: Duffy AG

PROVIDER: S-EPMC5074847 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

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The case for immune-based approaches in biliary tract carcinoma.

Duffy Austin G AG Makarova-Rusher Oxana V OV Greten Tim F TF

Hepatology (Baltimore, Md.) 20160618 5

Biliary tract cancers (BTC) comprise a group of uncommon malignancies in which the standard therapies are minimally effective and evolve slowly. Like the majority of gastrointestinal cancers, with some notable exceptions, the impact of immune-based approaches has yet to be seen. However, the etiological background of BTC-overlapping in almost every known causative or associated factor with inflammation-provides a strong clue that these approaches may have an impact in this group of diseases. Thi ...[more]

PMID: 27177447

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Project description:Purpose: To analyze human and bacteria proteomic profiles in bile, exposed to a tumor vs. non-tumor microenvironment, in order to identify differences between these conditions, which may contribute to a better understanding of pancreatic carcinogenesis. Patients and Methods: Using liquid chromatography and mass spectrometry, human and bacteria proteomic profiles of a total of 20 bile samples (7 from gallstone (GS) patients, and 13 from pancreatic head ductal adenocarcinoma (PDAC) patients) that were collected during surgery, and taken directly from the gallbladder were compared. g:Profiler and KEGG (Kyoto Encyclopedia of Genes and Genomes) Mapper Reconstruct Pathway was used as the main comparative platform focusing on over-represented biological pathways among human proteins and interaction pathways among bacterial proteins. Results: Three bacterial infection pathways were over-represented in the human PDAC group of proteins. IL-8 is the only human protein that coincides in the three pathways and this protein is only present in the PDAC group. Quantitative and qualitative differences in bacterial proteins suggest a dysbiotic microenvironment in the PDAC group, supported by significant participation of antibiotic biosynthesis enzymes. Prokaryote interaction signaling pathways highlight the presence of zeatin in the GS group and surfactin in the PDAC group, the former in the metabolism of terpenoids and polyketides, and the latter in both metabolisms of terpenoids, polyketides and quorum sensing. Based on our findings, we propose a bacterial-induced carcinogenesis model for the biliary tract. Conclusion: To the best of our knowledge this is the first study with the aim of comparing human and bacteria bile proteins in a tumor vs. non-tumor microenvironment. We proposed a new carcinogenesis model for the biliary tract based on bile metaproteomic findings. Our results suggest that bacteria may be key players in biliary tract carcinogenesis, in a long-lasting dysbiotic and epithelially harmful microenvironment, in which specific bacterial species biofilm formation is of utmost importance. Our finding should be further explored in future using in vitro and in vivo investigations

Dataset Information

The case for immune-based approaches in biliary tract carcinoma.

Publications

The case for immune-based approaches in biliary tract carcinoma.

Similar Datasets

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