American Association for Cancer Research
10780432ccr203655-sup-251625_3_supp_6873245_qnkjr1.docx (2.69 MB)

Supplementary Data from Spatial Analysis and Clinical Significance of HLA Class-I and Class-II Subunit Expression in Non–Small Cell Lung Cancer

Download (2.69 MB)
journal contribution
posted on 2023-03-31, 22:20 authored by Ila J. Datar, Sacha C. Hauc, Shruti Desai, Nicole Gianino, Brian Henick, Yuting Liu, Kostas Syrigos, David L. Rimm, Paula Kavathas, Soldano Ferrone, Kurt A. Schalper

Supplementary figures and tables.



Yale SPORE in Lung Cancer

Stand Up To Cancer – American Cancer Society Lung Cancer Dream Team Translational Research Grant

Department of Defense-Lung Cancer Research Program

Entertainment Industry Foundation



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). 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-naïve NSCLCs from four independent cohorts. Genomic analysis of HLA genes in NSCLC was performed using two publicly available cohorts. 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 <5% of lung malignancies. Tumors with cancer cell–specific β2M downregulation displayed reduced T cells and increased natural killer (NK)–cell infiltration. Samples with cancer cell HLA-A downregulation displayed modest increase in CD8+ T cells and NK-cell infiltration. Samples with cancer cell–selective HLA-B,-C or HLA class-II downregulation displayed reduced T cells and NK-cell infiltration. There was limited association of the markers with clinicopathologic variables and KRAS/EGFR mutations. Cancer cell–selective downregulation of the HLA subunits was associated with shorter overall survival. Our results reveal frequent and differential defects in HLA class-I and HLA class-II protein subunit expression in immunotherapy-naïve NSCLCs associated with distinct tumor microenvironment composition and patient survival.

Usage metrics

    Clinical Cancer Research





    Ref. manager