Measurement of immune cell-derived volatile organic compounds from ex vivo and in vitro cultures: a scoping review
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
Background:
Volatile organic compounds (VOCs) originate from cellular metabolic activity and disease-related biochemical processes and are emerging as non-invasive biomarkers. Although immune cells undergo marked metabolic and functional reprogramming during activation and
differentiation, their contribution to the cellular volatile metabolome remains poorly
characterised.
Aim of Review:
This scoping review aims to systematically map experimental studies reporting untargeted
VOCs emitted from mammalian immune cell cultures, with particular emphasis on volatilomics workflows and confidence in metabolite identification.
Key Scientific Concepts of Review:
A systematic literature search identified experimental studies analysing headspace VOCs from
primary and immortalised immune cells. Data were extracted on cell models, stimulation conditions, headspace sampling strategies, analytical platforms and data processing workflows. Analytical quality and confidence in compound assignment were assessed using the Chemical Analysis Working Group–Metabolomics Standards Initiative (CAWG-MSI)
criteria. Eleven studies met the inclusion criteria, employing a heterogeneous range of sampling and analytical approaches, including solid-phase microextraction, sorbent-based thermal desorption and secondary electrospray ionisation coupled to high-resolution mass spectrometry. Across studies, reported VOC profiles were able to distinguish immune cell type, activation state and external stimuli, supporting the biological plausibility of immune-derived volatilomic signatures. However, substantial methodological variability was evident. Only one study achieved CAWG-MSI level 1 identification, and most lacked key metadata,
internal standards or validation procedures. Overall, immune cells appear to emit distinct VOC signatures linked to immunometabolic state, but current practices limit reproducibility, cross-study comparability and confident biological interpretation. This review identifies
metabolomics-specific methodological priorities required to characterise immune-derived VOCs.
Volatile organic compounds (VOCs) originate from cellular metabolic activity and disease-related biochemical processes and are emerging as non-invasive biomarkers. Although immune cells undergo marked metabolic and functional reprogramming during activation and
differentiation, their contribution to the cellular volatile metabolome remains poorly
characterised.
Aim of Review:
This scoping review aims to systematically map experimental studies reporting untargeted
VOCs emitted from mammalian immune cell cultures, with particular emphasis on volatilomics workflows and confidence in metabolite identification.
Key Scientific Concepts of Review:
A systematic literature search identified experimental studies analysing headspace VOCs from
primary and immortalised immune cells. Data were extracted on cell models, stimulation conditions, headspace sampling strategies, analytical platforms and data processing workflows. Analytical quality and confidence in compound assignment were assessed using the Chemical Analysis Working Group–Metabolomics Standards Initiative (CAWG-MSI)
criteria. Eleven studies met the inclusion criteria, employing a heterogeneous range of sampling and analytical approaches, including solid-phase microextraction, sorbent-based thermal desorption and secondary electrospray ionisation coupled to high-resolution mass spectrometry. Across studies, reported VOC profiles were able to distinguish immune cell type, activation state and external stimuli, supporting the biological plausibility of immune-derived volatilomic signatures. However, substantial methodological variability was evident. Only one study achieved CAWG-MSI level 1 identification, and most lacked key metadata,
internal standards or validation procedures. Overall, immune cells appear to emit distinct VOC signatures linked to immunometabolic state, but current practices limit reproducibility, cross-study comparability and confident biological interpretation. This review identifies
metabolomics-specific methodological priorities required to characterise immune-derived VOCs.
Date Issued
2026-06-01
Date Acceptance
2026-04-19
Citation
Metabolomics, 2026, 22 (3)
ISSN
1573-3882
Publisher
Springer
Journal / Book Title
Metabolomics
Volume
22
Issue
3
Copyright Statement
© The Author(s) 2026. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/
License URL
Identifier
10.1007/s11306-026-02448-y
Publication Status
Published
Article Number
ARTN 75
Date Publish Online
2026-05-16