ORIGINAL RESEARCH article
Front. Oncol.
Sec. Thoracic Oncology
Volume 15 - 2025 | doi: 10.3389/fonc.2025.1640201
This article is part of the Research TopicMetabolism in the Tumour Microenvironment: Implications for Pathogenesis and TherapeuticsView all 6 articles
Linoleic acid drives pulmonary lymphoepithelioma-like carcinoma progression via PPAR-α/TF axis
Provisionally accepted
Hejing Bao1*
Jiani Zhang2Zhuoyan Chen2Yuhuan Wang2Zhe Wang2Zhiting Chen2Ting Jiang2Baishen Zhang3Wen Zeng4Hehong Bao5Shudong Ma2- 1Guangzhou Medical University, Guangzhou, China
- 2Southern Medical University Nanfang Hospital, Guangzhou, China
- 3Sun Yat-Sen University, Guangzhou, China
- 4Ganzhou People's Hospital, Ganzhou, China
- 5Chongqing University, Chongqing, China
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Primary pulmonary lymphoepithelioma-like carcinoma (pLELC) is a rare subtype of non-small cell lung cancer(NSCLC) with unclear etiological mechanisms. This study aimed to investigate the underlying molecular mechanisms and therapeutic targets for pLELC. Retrospectively collected samples from advanced pLELC patients underwent proteomic and metabolomic analyses, and patient-derived xenograft (PDX) models were established for validation. Data-independent acquisition (DIA) quantitative proteomics revealed upregulated tissue factor (TF) protein expression in pLELC, while untargeted metabolomics identified key metabolites such as linoleic acid (LA). Results demonstrated that LA promotes tumor progression by facilitating M2-type tumor-associated macrophage infiltration and suppressing natural killer (NK) cell activity, effects reversible by the TF inhibitor Tisotumab. Mechanistic studies indicated that LA enhances TF expression via peroxisome proliferator-activated receptor α (PPAR-α), and TF inhibitors effectively counteract LA-induced malignant phenotypes. This study reveals that LA remodels the pLELC tumor microenvironment through the PPAR-α/TF axis, suggesting TF as a potential therapeutic target for pLELC.
Keywords: Primary pulmonary lymphoepithelioma-like carcinoma, multiomics, Linoleic Acid, tissue factor, PPAR-α
Received: 19 Jun 2025; Accepted: 28 Jul 2025.
Copyright: © 2025 Bao, Zhang, Chen, Wang, Wang, Chen, Jiang, Zhang, Zeng, Bao and Ma. 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: Hejing Bao, Guangzhou Medical University, Guangzhou, China
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