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

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.