The correlation of HLA-A in Thai EGFR-mutated advanced non-small cell lung cancer, outcome, and tumor microenvironment

The correlation of HLA-A in Thai EGFR-mutated advanced non-small cell lung cancer, outcome, and tumor microenvironment

Abstract Previously reported HLA class I correlated with the outcome of early-stage non-small cell lung cancer (NSCLC) in the Japanese population. The binding affinity capability of the EGFR mutation peptide and various HLA-A subtypes could explain this. We conducted a prospective cohort study to ex...

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Main Authors: Nicha Zungsontiporn, Korakot Srianuwattipong, Sakun Santisukwongchote, Piyada Sitthideatphaiboon, Poonchavist Chantranuwat, Chatchawit Aporntewan, Chanida Vinayanuwattikun
Format: Article
Language:English
Published: Nature Portfolio 2025-08-01
Series:Scientific Reports
Subjects:
Tumor immune microenvironment
Advanced or recurrence NSCLC
EGFR mutations
HLA typing
EGFR TKIs
Online Access:https://doi.org/10.1038/s41598-025-16365-y
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Summary:Abstract Previously reported HLA class I correlated with the outcome of early-stage non-small cell lung cancer (NSCLC) in the Japanese population. The binding affinity capability of the EGFR mutation peptide and various HLA-A subtypes could explain this. We conducted a prospective cohort study to explore advanced EGFR-mutated NSCLC patients who received EGFR TKIs in various HLA-A subtypes, the outcomes of treatment, and tumor immune microenvironment (TIME). Eighty-four advanced NSCLC harboring EGFR exon 19 deletion and exon 21 L858R mutations were analyzed. Among these, the interested HLA-A subtypes of exon 19 deletion were composed of HLA-A*03:01 (7.1%), *30:01 (3.7%),*11:01 (82.1%), and *68:01 (7.1%). The interested HLA-A subtypes of exon 21 L858R were HLA-A*30:01 (28.5%), *33:03 (57.1%), and *34:01 (14.4%). Multivariate Cox-regression analysis revealed that the interested HLA-A subtypes were not an independent factor of progression-free or overall survival. No correlation was found between HLA-A subtypes and either inflammatory TIME or the presence of intra-tumoral CD8 TILs. HLA-A subtypes did not correlate with prognostic outcomes in sensitized EGFR mutations. The diverse binding affinity with EGFR peptides was not translated into the TIME patterns.
ISSN:2045-2322

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