Asthma and COPD are two respiratory disorders that have been linked to the IL-36 cytokines, a recently identified subset of the IL-1 family of cytokines. The purpose of this study was to look at the role of IL-36 cytokines in the pathogenesis of lung cancer in light of the shared aetiological ties between COPD and the emergence of lung cancer as well as the involvement of other IL-1 family members in the development of lung tumors. In this study, we show that lung cancer tissue expresses considerably higher levels of IL-36 cytokines and receptor mRNA and protein than does nearby non-tumor tissue. Two lung cancer cell lines, LLC murine lung cancer and SKMES-1 human squamous cell, were stimulated in in vitro tests. In all lung cancer cell lines, all IL-36 cytokines increased the expression of pro-inflammatory chemokines, and when cells were stimulated with IL-17, IL-22, and TNF, synergistic effects were observed. In addition, we reveal that the immune checkpoint inhibitor protein PD-L1 is expressed on lung cancer cells as a result of IL-36 cytokines. When considered as a whole, the data suggest that IL-36R signaling inhibition could be a beneficial targeted therapy for lung cancer patients with IL-36R+ cancer cells
