Genetic polymorphisms of IFNL3 are associated with risk of immune checkpoint inhibitor-related pneumonitis in lung cancer patients

IF 3.7 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Cytokine Pub Date : 2025-07-30 DOI:10.1016/j.cyto.2025.157002

Shengzu Peng , Zhihui Duan , Kai Zhang, Tao Lu, Guanghua Zheng

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Abstract

Background

Checkpoint inhibitor-related pneumonitis (CIP) is the most common fatal adverse reaction among lung cancer patients received immune checkpoint inhibitors (ICIs) therapy. IFN-λ3 has anti-tumor and immunomodulatory effects in lung cancer; however, little is known about the IFNL3 polymorphisms in CIP susceptible population.

Methods

Five candidate IFNL3 polymorphisms were genotyped in 102 CIP and 626 non-CIP lung cancer patients, and the serum level of IFN-λ3 was detected by ELISA among the participants.

Results

The minor allele rs12979860-T, rs12980275-G and rs8099917-G were correlated with 2.524, 3.158 and 3.932-fold raised risk of CIP, respectively (p < 0.001). Moreover, subgroup analysis according to tobacco use history showed that rs12980275 was correlated with CIP susceptibility in both subgroups, while rs12979860 and rs8099917 were associated with CIP in smokers (p < 0.005). Additionally, the serum concentration of IFN-λ3 in CIP group was obviously less than that in non-CIP group (p < 0.0001), and CIP patients with mutation genotypes of rs12979860, rs12980275 or rs8099917 had lower level of IFN-λ3 compared with those carriers with wild genotypes (p < 0.01).

Conclusion

IFNL3 rs129798060-TT, rs12980275-GG and rs8099917-GG genotypes were associated with lower serum level of IFN-λ3 and CIP susceptibility in lung cancer patients.

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IFNL3基因多态性与肺癌患者发生免疫检查点抑制剂相关性肺炎的风险相关

背景免疫检查点抑制剂相关性肺炎（CIP）是接受免疫检查点抑制剂（ICIs）治疗的肺癌患者中最常见的致命不良反应。IFN-λ3在肺癌中具有抗肿瘤和免疫调节作用；然而，对于CIP易感人群中IFNL3的多态性了解甚少。方法对102例CIP和626例非CIP肺癌患者的5个候选IFNL3多态性进行基因分型，并采用ELISA法检测血清IFN-λ3水平。结果小等位基因rs12979960 - t、rs12980275-G和rs8099917-G分别与CIP发病风险增高2.524倍、3.158倍和3.932倍相关(p <；0.001)。此外，根据烟草使用史进行亚组分析发现，rs12980275与两个亚组的CIP易感性相关，而rs12979860和rs8099917与吸烟者的CIP易感性相关(p <；0.005)。此外，CIP组血清IFN-λ3浓度明显低于非CIP组(p <；0.0001)， rs12979860、rs12980275、rs8099917基因型突变的CIP患者IFN-λ3水平低于野生基因型携带者(p <；0.01)。结论ifnl3 rs129798060-TT、rs12980275-GG和rs8099917-GG基因型与肺癌患者血清IFN-λ3水平降低及CIP易感性相关。

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来源期刊

Cytokine 医学-免疫学

CiteScore

7.60

自引率

2.60%

发文量

262

审稿时长

48 days

期刊介绍： The journal Cytokine has an open access mirror journal Cytokine: X, sharing the same aims and scope, editorial team, submission system and rigorous peer review. * Devoted exclusively to the study of the molecular biology, genetics, biochemistry, immunology, genome-wide association studies, pathobiology, diagnostic and clinical applications of all known interleukins, hematopoietic factors, growth factors, cytotoxins, interferons, new cytokines, and chemokines, Cytokine provides comprehensive coverage of cytokines and their mechanisms of actions, 12 times a year by publishing original high quality refereed scientific papers from prominent investigators in both the academic and industrial sectors. We will publish 3 major types of manuscripts: 1) Original manuscripts describing research results. 2) Basic and clinical reviews describing cytokine actions and regulation. 3) Short commentaries/perspectives on recently published aspects of cytokines, pathogenesis and clinical results.