Lung cancer brings heavy physical, mental and economic burden to patients worldwide due to the stubbornly high incidence and mortality [4]. Recently, the immune checkpoint inhibitors (ICIs) therapy has enriched the treatment of lung cancer and brought new hopes for clinical practice [14]. ICIs, mainly including inhibitors for programmed cell death protein 1 (PD-1) and its ligands PD-L1, can generate anti-tumor immune response by activating the immune system (mainly T cells) and have decent application effects [29]. However, in clinical applications, patients may experience systemic immune-related adverse reactions in the skin, gastrointestinal tract, liver, and lung [27]. Among them, checkpoint inhibitor-related pneumonitis (CIP) is the commonplace fatal adverse reaction, especially in lung cancer patients, the incidence can range from 9.5 % to 14.3 % [1]. At present, although many studies have analyzed the risk factors and prognostic characteristics of CIP through retrospective analysis of clinical data of patients, the pathogenesis of CIP remains unclear [10]. If the biomarkers for early identification of CIP can be screened, it may broaden the theoretical basis for management of the disease.

IFN-λ belongs to the type III interferon family. Although the receptors of IFN-λ are quite different from IFN-α/β family, their function are similar: both of them have strong antiviral and anti-tumor activities and immunomodulatory functions [16]. Studies have shown that IFN-λ has a broad spectrum of antiviral activity, including inhibition of influenza virus, neuroinvasive West Nile virus, human immunodeficiency virus, and other viruses, and with fewer side effects than IFN-α [12,15,19]. In addition, IFN-λ has been correlated with progression of a wide range of infectious diseases and development of inflammation. Due to the high expression of IFN-λ in the liver, the previous reports on IFN-λ mostly focuses on viral hepatitis, especially for hepatitis B virus (HBV) infection [25]. IFN-λ3 is the most active of the human IFN-λ family, it can induce IFN-stimulating genes more strongly than IFN-λ1/2, and has more significant antiviral effects [3]. Recent evidence revealed that IFN-λ3 could inhibit the expression of lung cancer-related NFκB signaling protein and NLRP3 complex, and can increase the activity of CD8+ cells, indicating the anti-tumor and immunomodulatory effects of IFN-λ3 in lung cancer [22,23]. Moreover, the mouse tumor-bearing model has further confirmed that IFN-λ3 can exert anti-tumor effects by regulating the tumor microenvironment, and thus can be utilized in tumor immunotherapy strategies [17]. However, it remains unclear whether IFN-λ3 levels are correlated with CIP.

Single nucleotide polymorphisms (SNPs) genotyping and analysis has been widely used in early screening of disease and individual-based treatment. Here, we chose five SNPs in IFN-λ3 encoding gene IFNL3 based on previous association studies and their minor allele frequencies (>5 %) in East Asian population. Previous studies have identified that the polymorphism of IFNL3 are associated with the infection and clearance of virus or IFN-λ3 level in patients. For instance, rs12979860 and rs12980275 were found to leukomonocyte level in patients with HBV-infection [32]. Rs8105790 was identified as a major predictor of antiviral therapeutic response in HCV patients [30]. Rs4803217 located in the 3’UTR of IFNL3 could affect HCV clearance by altering IFNL3 mRNA stability [26]. Moreover, rs8099917-TT was correlated with elevated IFN-λ3 level among hemodialysis patients [13]. However, none of the previous studies focused on these SNPs in lung cancer patients, especially in CIP groups. Considering the important role in antiviral response and immune regulation, we genotyped the five SNPs and detect the IFN-λ3 level among the CIP and non-CIP lung cancer patients in this study, and explored the correlation between the IFNL3 polymorphisms and CIP susceptibility.