Zungsontiporn Nicha, Srianuwattipong Korakot, Santisukwongchote Sakun, Sitthideatphaiboon Piyada, Chantranuwat Poonchavist, Aporntewan Chatchawit, Vinayanuwattikun Chanida
Division of Medical Oncology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and The King Chulalongkorn Memorial Hospital, Bangkok, Thailand.
Department of Pathology, Faculty of Medicine, Chulalongkorn University and The King Chulalongkorn, Memorial Hospital, Bangkok, Thailand.
Sci Rep. 2025 Aug 23;15(1):30989. doi: 10.1038/s41598-025-16365-y.
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-A30:01 (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.
先前报道称，在日本人群中，HLA-I类分子与早期非小细胞肺癌（NSCLC）的预后相关。表皮生长因子受体（EGFR）突变肽与各种HLA-A亚型的结合亲和力可能解释了这一点。我们进行了一项前瞻性队列研究，以探究接受EGFR酪氨酸激酶抑制剂（TKIs）治疗的不同HLA-A亚型的晚期EGFR突变NSCLC患者、治疗结果以及肿瘤免疫微环境（TIME）。对84例携带EGFR第19外显子缺失和第21外显子L858R突变的晚期NSCLC患者进行了分析。其中，第19外显子缺失的相关HLA-A亚型包括HLA-A*03:01（7.1%）、30:01（3.7%）、11:01（82.1%）和68:01（7.1%）。第21外显子L858R的相关HLA-A亚型为HLA-A30:01（28.5%）、33:03（57.1%）和34:01（14.4%）。多变量Cox回归分析显示，相关HLA-A亚型不是无进展生存期或总生存期的独立因素。未发现HLA-A亚型与炎性TIME或肿瘤内CD8+肿瘤浸润淋巴细胞（TILs）的存在之间存在相关性。HLA-A亚型与敏感型EGFR突变的预后结果无关。与EGFR肽的不同结合亲和力并未转化为TIME模式。
