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Updated: Dec 3, 2025
Predictive Immune Modeling of Solid Tumors
Published on: February 25, 2020
Microbiome-derived metabolome as a potential predictor of response to cancer immunotherapy
Agnieszka Beata Malczewski1,2,3, Severine Navarro4,5, Jermaine Ig Coward6,2
1Icon Cancer Centre, Wesley and South Brisbane, Brisbane, Queensland, Australia agnieszka.malczewski@icon.team.
Abstract:
Cancer immunotherapy with checkpoint blockade has become standard of care treatment for numerous cancer types. Despite this, robust predictive biomarkers are lacking. There is increasing evidence that the host microbiome is a predictor of immunotherapy response, although the optimal host microbiome has not been defined. Metabolomics is a new area of medicine that aims to analyze the metabolic profile of a biological system. The microbiome-derived metabolome (fecal and serum) represents the end products of microbial metabolism and these may be functionally more important than the distinct bacterial species that comprise a favorable microbiome. Short-chain fatty acids (SCFA) are metabolites produced by gut microbiota and have a role in T cell homeostasis, including differentiation of regulatory T cells. Recent studies have confirmed differential expression of SCFA for immunotherapy responders compared with non-responders. We propose that the microbiome metabolome, with a focus on SCFA may be a novel predictive biomarker for immunotherapy efficacy.
Insights
The microbiome metabolome, particularly short-chain fatty acids (SCFAs), may predict cancer immunotherapy success. Analyzing these microbial metabolites offers a new approach to identifying effective biomarkers for treatment response.
Area of Science:
- Oncology
- Immunology
- Microbiome research
Background:
- Cancer immunotherapy, specifically checkpoint blockade, is a standard treatment but lacks reliable predictive biomarkers.
- The host microbiome is increasingly recognized as a predictor of immunotherapy response, yet the ideal microbiome composition remains undefined.
- Metabolomics, the study of metabolic profiles, offers insights into biological systems.
Purpose of the Study:
- To investigate the potential of the microbiome-derived metabolome, focusing on short-chain fatty acids (SCFAs), as a predictive biomarker for cancer immunotherapy efficacy.
- To explore the functional significance of microbial metabolites over specific bacterial species in determining treatment outcomes.
Main Methods:
- Analysis of fecal and serum metabolomes to identify microbial metabolic end products.
- Focus on short-chain fatty acids (SCFAs), known metabolites produced by gut microbiota.
- Comparison of SCFA profiles between immunotherapy responders and non-responders.
Main Results:
- Short-chain fatty acids (SCFAs) are key metabolites produced by gut microbiota with roles in T cell homeostasis.
- Differential expression of SCFAs has been observed between patients who respond to immunotherapy and those who do not.
Conclusions:
- The microbiome metabolome, particularly SCFAs, presents a promising novel biomarker for predicting cancer immunotherapy efficacy.
- Metabolomic profiling may offer a more functionally relevant approach to biomarker discovery compared to analyzing bacterial species alone.
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