ORIGINAL RESEARCH article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1663362
This article is part of the Research TopicBeyond Conventional Biomarkers: Unlocking Immunotherapy Response Through Novel Biomarkers or Combinatorial ApproachesView all 5 articles
Serum Pyruvate and Lactate Predict Immunotherapy Efficacy in Advanced Gastric Cancer: A Prospective Biomarker Study
Provisionally accepted
- 1Nanjing Medical University, Nanjing, China
- 2Other
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Background: While immunotherapy has redefined clinical paradigms for advanced gastric cancer, reliable efficacy prediction remains a critical unmet challenge. Unlike invasive tissue-based predictors, circulating biomarkers offer non-invasive monitoring potential. This study investigated serum energy metabolites, whose dysregulation drove immune evasion, as predictors of therapeutic efficacy in advanced gastric cancer receiving first-line chemoimmunotherapy. Methods: We conducted a prospective observational study involving 52 patients with advanced gastric cancer receiving first-line chemoimmunotherapy. Serum metabolites of glycolysis and tricarboxylic acid (TCA) cycle were quantified via high-performance liquid chromatography-tandem mass spectrometry. Therapeutic response, progression-free survival (PFS), and overall survival (OS) were served as evaluation endpoints. Results: Patients exhibiting decreased serum concentrations of glycolytic metabolites (lactate and pyruvate) demonstrated significantly higher disease control rate (DCR) compared to those with elevated concentrations. Elevated serum lactate and pyruvate were significantly associated with inferior PFS and OS. Multivariate Cox regression established low lactate and pyruvate as independent prognostic factors for improved PFS and OS. However, no significant associations were observed between serum TCA cycle metabolites (citrate, isocitrate, α-ketoglutarate, succinate, fumarate, malate, and oxaloacetate) and DCR, PFS, or OS. Conclusion: Our findings suggest that serum lactate and pyruvate as non-invasive glycolytic biomarkers with high predictive utility for immunotherapy efficacy in advanced gastric cancer, requiring validation in larger cohorts to guide therapeutic decisions.
Keywords: Glycolytic metabolites, pyruvate, Lactate, Immunotherapy efficacy, gastric cancer, prospective study
Received: 10 Jul 2025; Accepted: 29 Aug 2025.
Copyright: © 2025 Liu, Dai, Wang, Wu and Wei. 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:
Jingjing Wu, Nanjing Medical University, Nanjing, China
Bin Wei, Nanjing Medical University, Nanjing, China
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