IntroductionThe germline HLA status has been implicated in immunotherapy outcome in non-small cell lung cancer (NSCLC) patients, but its correlation to immunotherapy-induced pneumonitis and prognostic impact in the Asian population remains largely unknown. MethodsWe examined the HLA genotype of the germline and available tumour samples in 42 patients with PD-L1 expression of >=50% undergoing pembrolizumab immunotherapy. The HLA allele expression was correlated with tumour response, disease survival and the occurrence of pneumonitis. ResultsIt was observed that the germline HLA-C homozygosity and HLA-DRB1*13 expression were related to a worse progression-free survival and treatment response. Importantly, all patients (7/7 patients) who developed pneumonitis in our cohort expressed the HLA-DPB1*02 allele, and the incidence of pneumonitis was 31.8% (7/22 patients) in patients expressing this allele compared to 0% (0/20 patients) in those without this allele (p = 0.009). Investigation of the tumour samples from 15 patients revealed that there was some degree of HLA loss in the HLA class I loci in 40% (6/15) of patients, and that no significant difference in tumour mutation burden was found among patients with different treatment response. ConclusionTaken together, this study examined the impact of HLA status in both germline and tumour samples in NSCLC patients with high PD-L1 expression, and the high incidence of immunotherapy-induced pneumonitis in patients expressing the HLA-DPB1*02 allele may suggest a routine HLA typing and closer monitoring in this patient subset.