The Emerging Role of IL-9 in the Anticancer Effects of Anti-PD-1 Therapy

PD-1 blockade rescues failing anticancer immune responses, resulting in durable remissions in some cancer patients. Cytokines such as IFN gamma and IL-2 contribute to the anti-tumor effect of PD-1 blockade. IL-9 was identified over the last decade as a cytokine demonstrating a potent ability to harness the anticancer functions of innate and adaptive immune cells in mice. Recent translational investigations suggest that the anticancer activity of IL-9 also extends to some human cancers. Increased T cell-derived IL-9 was proposed to predict the response to anti-PD-1 therapy. Preclinical investigations accordingly revealed that IL-9 could synergize with anti-PD-1 therapy in eliciting anticancer responses. Here, we review the findings suggesting an important contribution of IL-9 in the efficacy of anti-PD-1 therapy and discuss their clinical relevance. We will also discuss the role of host factors like the microbiota and TGF beta in the tumor microenvironment (TME) in the regulation of IL-9 secretion and anti-PD-1 treatment efficacy.

Automated summary

PD-1 blockade rescues failing anticancer immune responses and IL-9 plays an important role in the efficacy of this therapy in both mice and humans. IL-9 can synergize with anti-PD-1 therapy in eliciting anticancer responses. Host factors such as the microbiota and TGF beta in the tumor microenvironment also contribute to the regulation of IL-9 secretion and anti-PD-1 treatment efficacy.