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

Abstract

PD-1 blockade rescues failing anticancer immune responses, resulting in durable remissions in some cancer patients. Cytokines such as IFNγ 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 TGFβ in the tumor microenvironment (TME) in the regulation of IL-9 secretion and anti-PD-1 treatment efficacy.

Overcoming cold tumors: a combination strategy of immune checkpoint inhibitors

“…Similarly, in colorectal cancer, inhibiting TGF-β increases the number of cytotoxic T cells, thereby inhibiting tumor metastasis ( 45 ). Additionally, Interferon γ (IFNγ), Interleukin-2 (IL-2), and Interleukin-9 (IL-9) also play crucial roles in the efficacy of ICIs treatment ( 46 ).…”

Lighting Up the Fire in the Microenvironment of Cold Tumors: A Major Challenge to Improve Cancer Immunotherapy

“…The TGF-β blockade in combination with anti-PD-L1 treatment contributes to an increase in T cell infiltration and improvement in tumor regression in mouse models [ 41 ]. Besides TGF-β, IFNγ, IL-2, and IL-9 also contribute to the efficacy of anti-PD-1 therapy [ 43 ].…”