Spatial Analysis and Clinical Significance of HLA Class-I and Class-II Subunit Expression in Non–Small Cell Lung Cancer
抗原
医学
免疫组织化学
腺癌
CD8型
病理
作者
Ila Datar,Sacha C. Hauc,Shruti Desai,Nicole Gianino,Brian S. Henick,Yuting Liu,Konstantinos N. Syrigos,David L. Rimm,Paula B. Kavathas,Soldano Ferrone,Kurt A. Schalper
出处
期刊:Clinical Cancer Research [American Association for Cancer Research] 日期:2021-02-18卷期号:27 (10): 2837-2847被引量:3
标识
DOI:10.1158/1078-0432.ccr-20-3655
摘要
Purpose: To analyze the distribution, associated immune contexture, and clinical significance of human leukocyte antigen (HLA) class-I and HLA class-II subunits in non–small cell lung cancer (NSCLC). Experimental Design: Using spatially resolved and quantitative multiplexed immunofluorescence we studied the tumor/stromal tissue distribution, cancer cell–specific defects, and clinicopathologic/survival associations of β2 microglobulin (β2M), HLA-A, and HLA-B,-C heavy chains, as well as HLA class-II β chain in >700 immunotherapy-naive NSCLCs from four independent cohorts. Genomic analysis of HLA genes in NSCLC was performed using two publicly available cohorts. Results: Cancer cell–specific downregulation of HLA markers was identified in 30.4% of cases. β2M was downregulated in 9.8% (70/714), HLA-A in 9% (65/722), HLA-B,-C in 12.1% (87/719), and HLA class-II in 17.7% (127/717) of evaluable samples. Concurrent downregulation of β2M, HLA-B,-C, and HLA class-II was commonly identified. Deleterious mutations in HLA genes were detected in Conclusions: Our results reveal frequent and differential defects in HLA class-I and HLA class-II protein subunit expression in immunotherapy-naive NSCLCs associated with distinct tumor microenvironment composition and patient survival.