Williams Cancer Institute

THE ROLE OF TUMOR MICROBIOME DIVERSITY IN PANCREATIC CANCER SURVIVAL

THE ROLE OF TUMOR MICROBIOME DIVERSITY IN PANCREATIC CANCER SURVIVAL


Pancreatic ductal adenocarcinoma (PDAC) is a highly fatal disease with limited treatment options. Long-term survival in PDAC is uncommon, and factors influencing it are not well understood. While the genomic landscape is often linked to survival, recent research suggests the importance of the tumor microbiome and its potential role in patient outcomes. The gut microbiota, known to influence responses to therapies in other cancers, is also implicated in PDAC. Studies have shown the presence of specific bacteria in PDAC, affecting responses to chemotherapy.

In a study conducted by Riquelme et al. 2019, were employed a comprehensive methodology to investigate the influence of the tumor microbiome on pancreatic ductal adenocarcinoma (PDAC) outcomes. Tumor and gut microbiome profiles were analyzed through 16S rRNA gene sequencing, metagenomic shotgun sequencing, and computational techniques. The identification of microbial signatures associated with long-term and short-term PDAC survival involved statistical analyses. Additionally, the study utilized mouse models for fecal microbiota transplantation experiments, confirming the impact of the gut microbiome on the tumor microbiome and its subsequent effects on immune response and tumor growth. Various molecular and imaging techniques were employed to validate the presence of bacteria in tumors. This multi-pronged approach strengthened the study’s insights into the complex interplay between the microbiome and PDAC prognosis.

Long-term survivors (LTS) exhibited higher microbial diversity in tumors compared to short-term survivors (STS). Distinct microbial signatures were identified in LTS and STS, with specific bacterial genera such as Saccharopolyspora, Pseudoxanthomonas, and Streptomyces being significantly associated with a more active immune response and increased survival. The presence of bacteria in tumors was confirmed using various techniques. The composition of the gut microbiome also influenced the tumor microbiome, and fecal transfer from LTS-NED patients to mice positively impacted the tumor microbiome, activated the immune response, and reduced tumor growth. These findings underscore the relevance of the microbiome in PDAC outcomes, suggesting potential prognostic and therapeutic applications.

The study underscores the significance of the tumor microbiome in PDAC outcomes. Microbial diversity and specific bacterial communities within tumors, particularly in long-term survivors, correlate with immune responses and patient survival. Manipulating the gut microbiome through FMT has the potential to modify the tumor microbiome, influence immune responses, and impact tumor growth. Understanding these microbiome interactions opens avenues for prognostic tools and therapeutic strategies in PDAC, addressing a critical unmet need in the field.

Reference: Erick Riquelme, Yu Zhang, Liangliang Zhang, Maria Montiel, Michelle Zoltan, Wenli Dong, Pompeyo Quesada, Ismet Sahin, Vidhi Chandra, Anthony San Lucas, Paul Scheet, Hanwen Xu, Samir M. Hanash, Lei Feng, Jared K. Burks, Kim-Anh Do, Christine B. Peterson, Deborah Nejman, Ching-Wei D. Tzeng, Michael P. Kim, Cynthia L. Sears, Nadim Ajami, Joseph Petrosino, Laura D. Wood, Anirban Maitra, Ravid Straussman, Matthew Katz, James Robert White, Robert Jenq, Jennifer Wargo, Florencia McAllister, 08 August 2019, Tumor Microbiome Diversity and Composition Influence Pancreatic Cancer Outcomes, https://doi.org/10.1016/j.cell.2019.07.008

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