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Updated: Dec 29, 2025
Predictive Immune Modeling of Solid Tumors
Published on: February 25, 2020
Gut metabolomics profiling of non-small cell lung cancer (NSCLC) patients under immunotherapy treatment
Andrea Botticelli1,2, Pamela Vernocchi3, Federico Marini4,5
1Department of Clinical and Molecular Medicine, Sapienza University of Rome, Rome, Italy.
Background:
Despite the efficacy of immune checkpoint inhibitors (ICIs) only the 20-30% of treated patients present long term benefits. The metabolic changes occurring in the gut microbiota metabolome are herein proposed as a factor potentially influencing the response to immunotherapy.
Methods:
The metabolomic profiling of gut microbiota was characterized in 11 patients affected by non-small cell lung cancer (NSCLC) treated with nivolumab in second-line treatment with anti-PD-1 nivolumab. The metabolomics analyses were performed by GC-MS/SPME and 1H-NMR in order to detect volatile and non-volatile metabolites. Metabolomic data were processed by statistical profiling and chemometric analyses.
Results:
Four out of 11 patients (36%) presented early progression, while the remaining 7 out of 11 (64%) presented disease progression after 12 months. 2-Pentanone (ketone) and tridecane (alkane) were significantly associated with early progression, and on the contrary short chain fatty acids (SCFAs) (i.e., propionate, butyrate), lysine and nicotinic acid were significantly associated with long-term beneficial effects.
Conclusions:
Our preliminary data suggest a significant role of gut microbiota metabolic pathways in affecting response to immunotherapy. The metabolic approach could be a promising strategy to contribute to the personalized management of cancer patients by the identification of microbiota-linked "indicators" of early progressor and long responder patients.
Insights
Gut microbiota metabolites impact immunotherapy response in lung cancer patients. Specific metabolites like SCFAs indicate long-term benefits, while others are linked to early progression, aiding personalized cancer treatment.
Area of Science:
- Oncology
- Immunotherapy
- Microbiome Research
- Metabolomics
Background:
- Immune checkpoint inhibitors (ICIs) benefit only 20-30% of patients long-term.
- Gut microbiota metabolome alterations may influence immunotherapy response.
Purpose of the Study:
- To investigate the association between gut microbiota metabolomic profiles and immunotherapy response in non-small cell lung cancer (NSCLC).
Main Methods:
- Metabolomic profiling of gut microbiota in 11 NSCLC patients treated with nivolumab.
- GC-MS/SPME and 1H-NMR used for volatile and non-volatile metabolite detection.
- Statistical and chemometric analyses applied to metabolomic data.
Main Results:
- 36% of patients showed early progression, 64% had long-term benefits (>12 months).
- 2-Pentanone and tridecane associated with early progression.
- Short-chain fatty acids (SCFAs), lysine, and nicotinic acid associated with long-term benefits.
Conclusions:
- Gut microbiota metabolic pathways significantly influence immunotherapy response.
- Metabolic profiling can identify indicators for personalized cancer patient management.
- This approach may help distinguish early progressors from long responders.
