A Comprehensive Review of the Current and Future Role of the Microbiome in Pancreatic Ductal Adenocarcinoma

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is expected to become the second most common cause of cancer death in the USA by 2030, yet progress continues to lag behind that of other cancers, with only 9% of patients surviving beyond 5 years. Long-term survivorship of PDAC and improving survival has, until recently, escaped our understanding. One recent frontier in the cancer field is the microbiome. The microbiome collectively refers to the extensive community of bacteria and fungi that colonise us. It is estimated that there is one to ten prokaryotic cells for each human somatic cell, yet, the significance of this community in health and disease has, until recently, been overlooked. This review examines the role of the microbiome in PDAC and how it may alter survival outcomes. We evaluate the possibility of employing microbiomic signatures as biomarkers of PDAC. Ultimately this review analyses whether the microbiome may be amenable to targeting and consequently altering the natural history of PDAC.

Fungi and cancer

“…Re-colonising antifungal-treated tumour-bearing mice with M. globosa or Alternaria alternata promoted tumour growth and could trigger IL-33 secretion, inducing a type 2 immune response that possibly accelerated pancreatic cancer development. This further suggests a role of intratumoral fungi or remotely secreted fungal products in pancreatic carcinogenesis, which is reviewed in more detail elsewhere 119…”

Immunotherapy Perspectives for Pancreatic Ductal Adenocarcinoma (PDAC)

“…vaccines, Granulocyte-Macrophage Colony-Stimulating Factor (GMCSF)-allogeneic pancreatic tumor cells (GVAX) vaccines, and Hyper-Acute-Pancreas algenpantucel-L (HAPa), Mucin-1 (MUC-1) vaccines can be mentioned (4)(5)(6). Adoptive cell therapy is a rapidly growing technology consisting of NK cells or T cells that are either allogeneic or autologous.…”

Impact of gut microbiome in the development and treatment of pancreatic cancer: Newer insights

“…As evidence by the work of Riquelme et al [ 84 ], Fecal Microbiotal Transplant from human subjects to mice, yielded from PC long term murine survivors, showed a significant reduction in tumor growth, however, that effect was lost with the use of antibiotics altering the fecal microbiota[ 84 , 85 ]. Furthermore, it was found that long term survivor mice that did not receive antibiotics were rich in CD8+ T-cell, enhancing the tumor immune cell infiltration.…”

“…Furthermore, it was found that long term survivor mice that did not receive antibiotics were rich in CD8+ T-cell, enhancing the tumor immune cell infiltration. On the other hand, mice that were treated with antibiotics, thus altering the fecal microbiota, showed an increased number of CD4+FOXP3+ T-regs and myeloid derived suppressor cells which are well known to lower the immune system, thus promoting tumor growth[ 84 , 85 ].…”