Chronic inflammation drives the progression of colorectal cancer (CRC).
Increased expression of interleukin (IL)-17A is associated with poor prognosis,
and IL-17A blockade curbs tumor progression in preclinical models of CRC. Here
we examined the impact of IL-1 signaling, a key regulator of the IL-17 pathway,
in different cells types within the CRC microenvironment. Genetic deletion of
the IL-1 receptor (IL-1R1) in epithelial cells alleviated tumorigenesis in the
APC model of CRC, demonstrating a cell-autonomous role for IL-1 signaling in
early tumor seed outgrowth. T cell specific ablation of IL-1R decreased
tumor-elicited inflammation dependent on IL-17 and IL-22, thereby reducing CRC
progression. The pro-tumorigenic roles of IL-1 were counteracted by its effects
on myeloid cells, particularly neutrophils, where IL-1R1 ablation resulted in
bacterial invasion into tumors, heightened inflammation and aggressive CRC
progression. Thus, IL-1 signaling elicits cell type-specific responses which, in
aggregate, set the inflammatory tone of the tumor microenvironment and determine
the propensity for disease progression.