The complex roles of IL-36 and IL-38 in cancer: friends or foes?

The interleukin-36 (IL-36) family comprises of three pro-inflammatory receptor agonists (IL-36α, IL-36β and IL-36γ), two anti-inflammatory receptor antagonists (IL-36RA and IL-38) along with the IL-36 receptor (IL-36R). Part of the IL-1 cytokine superfamily, the IL-36 family was discovered in the early 2000s due to the homology of its member sequences to the IL-1 cytokines. As pro- and anti-inflammatory cytokines, respectively, IL-36α, IL-36β, IL-36γ and IL-38 aid in maintaining homoeostasis by reciprocally regulating the body's response to damage and disease through IL-36R-associated signalling.

IL-36 expression is increased in NSCLC with IL-36 stimulation of lung cancer cells promoting a pro-tumorigenic phenotype.

The IL-36 cytokines are a recently described subset of the IL-1 family of cytokines, and have been shown to play a role in the pathogenesis of respiratory diseases such as asthma and COPD. Given the common aetiological links between COPD and lung cancer development, as well as the involvement of other IL-1 family members in lung tumorigenesis, the aim of this work was to investigate the role of IL-36 cytokines in the pathogenesis of lung cancer. In this study we demonstrate that expression of IL-36 cytokines and receptor mRNA and protein are significantly increased in lung cancer tissue compared to adjacent non-tumour tissue.