Figure 1.

Commensal microbiota influence malignant progression of extraintestinal tumors by TLR5-driven modulation of the systemic tumor macroenvironment. In TLR5-responsive hosts bearing IL-6 responsive tumors, elevated systemic levels of IL-6 drive an accumulation of myeloid-derived suppressor cells (MDSCs) producing adenosine and the subsequent induction of galectin-1 expression in tumor-associated γδ T cells. This leads to significant suppression of antitumor immunity and accelerated malignant progression. TLR5-deficient tumor-bearing hosts have elevated systemic levels of IL-17, which is the dominant tumor-promoting cytokine in the absence of IL-6, when hosts are bearing IL-6 nonresponsive tumors. Differences in malignant progression are dependent on TLR5-mediated signaling and the commensal microbiota at barrier surfaces.