Pancreatic ductal adenocarcinoma (PDAC) is one of the leading causes of cancer-related death. This is attributable to many factors culminating in a lack of response to surgery, chemo- and immunotherapies. The lack of response to immunotherapy is despite the fact that PDAC exhibits a significant immune infiltrate. Relatively little is understood about the immune landscape in PDAC, but it is clear that suppressive populations of macrophages likely play a key role in shaping the tumor microenvironment and targeting them could alter immunity improving therapeutic responses. Likewise, altered microbiome activity has been linked to pancreatic cancer progression, resistance to immune therapy, and survival times in patients. Recently we described a critical role for the aryl hydrocarbon receptor (AhR) as a driver of macrophage suppressive polarization. Since AhR is an essential sensor of microbial metabolites, we surmised that the microbiome may drive tumor macrophage function via the metabolic products produced by the flora; while blocking AhR activity would cause the tumor microenvironment to become “hot” enhancing responses to standard-of-care chemotherapy and immunotherapy. Our data demonstrate that AhR is critical for tumor growth and specific metabolites produced by the microbiome drive macrophage suppressive function. Thus, the results identify a key new mechanistic link between microbiome:tumor immune micro environment interactions that fosters growth and immune therapy resistance.