Cancer cells induce interleukin-22 production from memory CD4 ⁺ T cells via interleukin-1 to promote tumor growth

Abstract

Significance IL-22 has been identified as a cancer-promoting cytokine, but its regulation in cancer tissue has not been addressed. Using both murine and human models, we demonstrate that cancer cells directly induce IL-22 production. We prove that interleukin-1β induced by inflammasome activation is critical for IL-22 production. IL-1β increased the activity of the IL-22 transcription factors in lineage-committed T cells. We show the existence of IL-22–producing Th1, Th17, and Th22 cells in tumor tissue of patients. Use of the clinically approved IL-1 receptor antagonist anakinra in vivo reduced IL-22 production and reduced tumor growth in a breast cancer model. These data provide the basis for therapeutic interventions, particularly using anakinra, aiming at limiting IL-22 production in patients with cancer.