학술논문

Biomarkers of Immunotherapy Response in Patients with Non-Small-Cell Lung Cancer: Microbiota Composition, Short-Chain Fatty Acids, and Intestinal Permeability.
Document Type
Article
Source
Cancers. Mar2024, Vol. 16 Issue 6, p1144. 15p.
Subject
*FECAL analysis
*RISK assessment
*SHORT-chain fatty acids
*RESEARCH funding
*DRUG side effects
*GUT microbiome
*INTESTINAL barrier function
*IMMUNOTHERAPY
*TUMOR markers
*TREATMENT effectiveness
*CANCER patients
*IMMUNE checkpoint inhibitors
*AMINO acids
*LUNG cancer
*IMMUNITY
*ENDOTOXINS
Language
ISSN
2072-6694
Abstract
Simple Summary: There is evidence of the influence of the intestinal microbiota on the response to immunotherapy in cancer. In addition, we lack markers of response to treatment and toxicity, which obliges us to continue our search for them. In this work, we recruited patients with non-small-cell lung cancer receiving immunotherapy who contributed a fecal and blood sample. We analyzed the possible relationship between the response to immune checkpoint inhibitors and the occurrence of immune-related adverse events, the composition (16S rDNA amplification) and functionality (abundance of short-chain fatty acids) of the gut microbiota, and intestinal membrane permeability as a human factor. No correlations were detected between analytical markers and clinical evolution, with a marked individuality of the gut microbiota in terms of composition, but homogeneity in its functionality and permeability. 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. [ABSTRACT FROM AUTHOR]