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ORIGINAL RESEARCH article
Front. Immunol.
Sec. Vaccines and Molecular Therapeutics
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1564731
This article is part of the Research Topic Lung Adenocarcinoma: From Genomics to Immunotherapy, Volume II View all 8 articles
Identification of new HLA-A*0201-restricted cytotoxic T lymphocyte epitopes from LDHC in lung adenocarcinoma
Provisionally accepted
Ruifang Zhong 1 Xiaohong Guo 1 Chuncai Wu 1 Yangyi Guo 2
Yanli Kang 1
Jianbin You 3
Falin Chen 1,3 Qianshun Chen 3
Liangyuan Chen 1,3*- 1 Fujian Medical University, Fuzhou, Fujian Province, China
- 2 Third Hospital of Longyan, Longyan, Fujian Province, China
- 3 Fujian Provincial Hospital, Fuzhou, China
Background: Lactate dehydrogenase C (LDHC) is a kind of cancer-testis antigen (CTA), which has been reported to be a biomarker for the diagnosis, efficacy evaluation, and recurrence monitoring for lung adenocarcinoma (LUAD). This study aims to access the value of LDHC in peptide-based vaccine for LUAD immunotherapy.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 to 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 cells lysis ability of peptides-induced specific cytotoxic T lymphocytes (CTLs).The LDHC recombinant protein promoted invasion and migration of PC9 cells. Three HLA-A2 restricted LDHC-derived peptides P2 (LDHC 170-180 , FRYLIGEKLGV), P5 (LDHC 116-124 , IMKSIIPAI) and P6 (LDHC 172-180 , YLIGEKLGV) had a high affinity with HLA-A2 molecule at 50μg/mL. P6 (LDHC 172- 180 , 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.
Keywords: Lung Adenocarcinoma, HLA-A2, Lactate dehydrogenase c, recombinant protein, Peptides
Received: 22 Jan 2025; Accepted: 19 Mar 2025.
Copyright: © 2025 Zhong, Guo, Wu, Guo, Kang, You, Chen, Chen and Chen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Liangyuan Chen, Fujian Provincial Hospital, Fuzhou, China
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.