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Biomarkers of Immunotherapy Response in Patients with Non-Small-Cell Lung Cancer: Microbiota Composition, Short-Chain
Alba Moratiel-Pellitero1, María Zapata-García1, Marta Gascón-Ruiz2
1Medical Oncology Department, University Hospital Lozano Blesa, Institute for Health Research Aragón, 50009 Zaragoza, Spain.
Abstract:
Immune checkpoint inhibitors have been proposed as the standard treatment for different stages of non-small-cell lung cancer in multiple indications. Not all patients benefit from these treatments, however, and certain patients develop immune-related adverse events. Although the search for predictors of response to these drugs is a major field of research, these issues have yet to be resolved. It has been postulated that microbiota could play a relevant role in conditioning the response to cancer treatments; however, the human factor of intestinal permeability also needs to be considered as it is closely related to the regulation of host-microbiota interaction. In this article, we analyzed the possible relationship between the response to immune checkpoint inhibitors and the onset of immune-related adverse events, gut microbiota status, and intestinal membrane permeability. In a pioneering step, we also measured short-chain fatty acid content in feces. Although the correlation analyses failed to identify predictive biomarkers, even when all variables were integrated, our patients' microbial gut ecosystems were rich and diverse, and the intestinal barrier's integrity was preserved. These results add new knowledge on the composition of microbiota and its correlation with barrier permeability and short-chain fatty acids and suggest that more studies are required before these potential biomarkers can be incorporated into the clinical management of patients via immune checkpoint inhibitor treatment.
Insights
This study explored gut microbiota, intestinal permeability, and short-chain fatty acids as biomarkers for immune checkpoint inhibitor response in non-small-cell lung cancer. While no predictive biomarkers were identified, findings highlight preserved gut health in patients.
Area of Science:
- Oncology
- Immunology
- Microbiome Research
Background:
- Immune checkpoint inhibitors (ICIs) are standard for non-small-cell lung cancer (NSCLC), but response and adverse events vary.
- Predictors for ICI efficacy and toxicity remain elusive.
- The gut microbiota and intestinal permeability are implicated in modulating host response to cancer therapies.
Purpose of the Study:
- To investigate the relationship between gut microbiota, intestinal permeability, and immune-related adverse events (irAEs) in NSCLC patients treated with ICIs.
- To explore short-chain fatty acid (SCFA) profiles as potential biomarkers.
- To assess the correlation between these factors and treatment response.
Main Methods:
- Analysis of gut microbiota composition and diversity.
- Assessment of intestinal membrane permeability.
- Measurement of fecal short-chain fatty acid (SCFA) content.
- Correlation analyses integrating microbiota, permeability, and SCFA data with ICI response and irAEs.
Main Results:
- No significant correlation was found between gut microbiota, intestinal permeability, SCFA levels, and ICI response or irAEs.
- Patients exhibited rich and diverse gut microbial ecosystems.
- Intestinal barrier integrity was preserved in the studied cohort.
Conclusions:
- Current analyses did not identify predictive biomarkers for ICI treatment in NSCLC based on gut microbiota, permeability, or SCFAs.
- The findings contribute to understanding the interplay between gut health and ICI therapy.
- Further research is needed to validate potential biomarkers for clinical application in ICI treatment.
