Williams Cancer Institute

FMT AND PANCREATIC CANCER: UNVEILING NEW PATHS FOR IMMUNOTHERAPY

FMT AND PANCREATIC CANCER: UNVEILING NEW PATHS FOR IMMUNOTHERAPY


In a groundbreaking clinical trial, researchers led by Dr. Florencia McAllister of the MD Anderson Cancer Center are embarking on an innovative exploration to assess the impact of fecal microbial transplants (FMT) on the unique tumor microbiome of patients with pancreatic ductal adenocarcinoma (PDAC). This trial, presented at the virtual conference on pancreatic cancer hosted by the American Association for Cancer Research (AACR), represents the first attempt to investigate whether FMT can alter the tumor microenvironment, potentially rendering stubborn tumors more receptive to immunotherapy.

Pancreatic cancer, particularly PDAC, stands as one of the most aggressive malignancies with a 5-year survival rate of approximately 9%. The limitations of current therapies, including immunotherapy, have prompted the exploration of unconventional avenues. The trial builds upon years of pre-clinical studies, revealing promising results indicating that FMT from healthy donors or PDAC survivors led to reduced immunosuppression and diminished tumor growth in mice with human pancreatic tumors.

The clinical trial will involve ten PDAC patients scheduled for surgery, with tumor tissue analysis conducted both before FMT and one year post-surgery. The aim is to evaluate whether the bacterial composition of the tumor microenvironment undergoes changes following FMT. The study will include adult patients with resectable PDAC, utilizing FMT from healthy donors administered through colonoscopy and oral pills, marking the first-ever trial of its kind for pancreatic cancer.

Pancreatic cancer’s formidable nature, coupled with limited efficacy from existing therapies, has fueled the quest to unravel the mysteries behind the disease. Preliminary investigations have uncovered a potential link between microbial host factors and prolonged survival, prompting a closer examination of the tumor microbiome.

Studies comparing long-term survivors with short-term survivors revealed a greater microbial diversity and distinct bacterial species in the tumors of those with extended survival. Notably, the presence of specific bacteria predicted better outcomes, offering a potential microbial signature for long-term survival. Subsequent analysis suggested a connection between the gut microbiome and the tumor microbiome, indicating that changes in the gut may reflect within the tumor.

Pre-clinical mouse models demonstrated that FMT from long-term survivors had a protective effect against tumors, emphasizing the potential impact of gut and tumor bacteria on disease progression. Further investigations implicated interleukin-17 (IL-17) in triggering and sustaining immunosuppression, providing a potential target for intervention.

The trial’s goal is to determine whether gut microbes from healthy individuals can influence the tumor microenvironment in PDAC patients, potentially reversing the immune suppression characteristic of the disease. If successful, this novel approach could pave the way for more effective immunotherapy strategies in the challenging landscape of pancreatic cancer.

The exploration of fecal microbial transplants in the context of pancreatic cancer represents a pioneering endeavor that holds promise for transforming the treatment paradigm. By unraveling the intricate relationship between the gut microbiome, tumor microbiome, and immune response, researchers aim to offer a glimmer of hope for patients facing the formidable challenges of pancreatic ductal adenocarcinoma.

Reference: Froelich, Warren. The Role of Fecal Microbial Transplants in Pancreatic Cancer, November 20, 2020. | https://journals.lww.com/oncology-times/fulltext/2020/11200/the_role_of_fecal_microbial_transplants_in.13.aspx

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