HLA-I genotype landscape in lung cancer and its prognosis value in Chinese small cell lung cancer

The human leukocyte antigen class I (HLA-I) genotypes have been proven to have an impact on the oncogenic mutational landscape and immunotherapy outcomes in several cancers. However, the HLA-I genotype landscape and its implications for lung cancer remain largely unknown. In this study, whole blood samples from 400 Chinese lung cancer patients were subjected to DNA sequencing for the detection of HLA-I genotypes. RNA sequencing data from 32 SCLC primary tumors were analyzed for immune cell infiltration and activity. Additionally, we collected HLA-I genotype and transcriptome data from 445 LUAD and 430 LUSC patients from The Cancer Genome Atlas (TCGA) database for comparisons. The proportion of HLA supertypes was similar among lung cancer patients with different pathological types but different among patients of different races. Chinese SCLC patients with the B44 supertype had more potent cytolytic activity and increased expression of MHC-II genes, interferon-gamma (IFN-γ), and chemokine signature genes than Chinese patients with other supertypes. Moreover, increased expression levels of immune checkpoint molecules were observed in tumors from B44(+) patients. Most importantly, we analyzed the correlation between the HLA supertype and prognosis and found that the positive effect of the HLA-B44 supertype on PFS verifies the prognostic value of HLA-B44 in SCLC. In conclusion, this study is among the first to depict the landscape of HLA-I genotypes in lung cancer patients. Comprehensive analysis revealed the effect of the B44 supertype on the tumor immune microenvironment and survival outcome of Chinese SCLC patients, providing fresh insight for the treatment of SCLC.