The past decade has witnessed groundbreaking advances in the field of microbiome research. An area where immense implications of the microbiome have been demonstrated is tumor biology. The microbiome affects tumor initiation and progression through direct effects on the tumor cells and indirectly through manipulation of the immune system. It can also determine response to cancer therapies and predict disease progression and survival. Modulation of the microbiome can be harnessed to potentiate the efficacy of immunotherapies and decrease their toxicity. In this review, we comprehensively dissect recent evidence regarding the interaction of the microbiome and anti-tumor immune machinery and outline the critical questions which need to be addressed as we further explore this dynamic colloquy.

Pancreatic ductal adenocarcinoma (PDAC) is a leading cause of cancer-related morbidity and mortality in the western world, with limited therapeutic strategies and dismal long-term survival. Cancer-associated fibroblasts (CAFs) are key components of the pancreatic tumor microenvironment, maintaining the extracellular matrix, while also being involved in intricate crosstalk with cancer cells and infiltrating immunocytes. Therefore, they are potential targets for developing therapeutic strategies against PDAC. However, recent studies have demonstrated significant heterogeneity in CAFs with respect to their origins, spatial distribution, and functional phenotypes within the PDAC tumor microenvironment. Therefore, it is imperative to understand and delineate this heterogeneity prior to targeting CAFs for PDAC therapy.