从肺腺癌中的乳酸脱氢酶C（LDHC）鉴定新的HLA-A*0201限制性细胞毒性T淋巴细胞表位
Identification of new HLA-A*0201-restricted cytotoxic T lymphocyte epitopes from LDHC in lung adenocarcinoma.
作者信息
Zhong Ruifang, Guo Xiaohong, Wu Chuncai, Guo Yangyi, Kang Yanli, You Jianbin, Chen Falin, Chen Qianshun, Chen Liangyuan
机构信息
Shengli Clinical Medical College of Fujian Medical University, Fuzhou, China.
Department of Clinical Laboratory, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, China.
出版信息
Front Immunol. 2025 Apr 9;16:1564731. doi: 10.3389/fimmu.2025.1564731. eCollection 2025.
BACKGROUND
Lactate dehydrogenase C (LDHC) is a kind of cancer-testis antigen (CTA) that has been reported to be a biomarker for diagnosis, efficacy evaluation, and recurrence monitoring of lung adenocarcinoma (LUAD). This study aims to assess the value of LDHC in peptide-based vaccines for LUAD immunotherapy.
METHODS
The LDHC recombinant protein was purified and its effect on PC9 cells was evaluated by wound healing assay, Transwell invasion, and migration assay. Ten HLA-A2-restricted LDHC-derived peptides were predicted and synthesized, and the affinity for the HLA-A2 molecule was analyzed by T2 binding assay and molecule docking. Enzyme-linked immunospot (ELISpot) and LDH cytotoxicity assay were performed to determine the interferon-γ (IFN-γ) release level and tumor cell lysis ability of peptide-induced specific cytotoxic T lymphocytes (CTLs).
RESULTS
The LDHC recombinant protein promoted invasion and migration of PC9 cells. Three HLA-A2-restricted LDHC-derived peptides P2 (LDHC, FRYLIGEKLGV), P5 (LDHC, IMKSIIPAI), and P6 (LDHC, YLIGEKLGV) had high affinity for the HLA-A2 molecule at 50 μg/mL. P6 (LDHC, YLIGEKLGV) elicited the strongest IFN-γ-secreting cytotoxic T lymphocyte (CTL) response and exhibited potent cytotoxicity against HLA-A2-positive cells with high LDHC expression.
CONCLUSIONS
LDHC may serve as a targetable biomarker for peptide-based immunotherapy of LUAD.
背景
乳酸脱氢酶C（LDHC）是一种癌胚抗原（CTA），据报道是肺腺癌（LUAD）诊断、疗效评估和复发监测的生物标志物。本研究旨在评估LDHC在基于肽的LUAD免疫治疗疫苗中的价值。
方法
纯化LDHC重组蛋白，并通过伤口愈合试验、Transwell侵袭和迁移试验评估其对PC9细胞的作用。预测并合成了10种HLA - A2限制性LDHC衍生肽，通过T2结合试验和分子对接分析其与HLA - A2分子的亲和力。进行酶联免疫斑点（ELISpot）和LDH细胞毒性试验，以确定肽诱导的特异性细胞毒性T淋巴细胞（CTL）的干扰素-γ（IFN-γ）释放水平和肿瘤细胞裂解能力。
结果
LDHC重组蛋白促进了PC9细胞的侵袭和迁移。三种HLA - A2限制性LDHC衍生肽P2（LDHC，FRYLIGEKLGV）、P5（LDHC，IMKSIIPAI）和P6（LDHC，YLIGEKLGV）在50μg/mL时对HLA - A2分子具有高亲和力。P6（LDHC, YLIGEKLGV）引发了最强的分泌IFN-γ的细胞毒性T淋巴细胞（CTL）反应，并对高表达LDHC的HLA - A2阳性细胞表现出强大的细胞毒性。
结论
LDHC可能作为LUAD基于肽的免疫治疗的可靶向生物标志物。
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