Harvard Study Links Gut Microbiota to Cancer Immunotherapy Response and Side Effects
Researchers at Harvard Medical School and Massachusetts General Hospital have uncovered key links between gut microbiota and adverse events, as well as response to combined CTLA-4 and PD-1 blockade treatment in cancer patients. Their findings, published in Nature Medicine, suggest potential new approaches to manage immunotherapy side effects and enhance treatment efficacy.
The study identified specific intestinal microbiota signatures that correlate with high-grade adverse events and treatment response. Notably, non-responders exhibited a higher level of copy number loss, predominantly affecting chromosomes 5, 10, and 15. Additionally, patients who experienced severe adverse events (grade 3 or higher) displayed a more diverse T cell repertoire and a more naïve T cell phenotype in their systemic circulation.
Intriguingly, certain bacterial species played significant roles. A higher abundance of Bacteroides intestinalis was linked to increased mucosal IL-1β and associated inflammation, as well as toxicity from combined immunotherapy. Conversely, Parabacteroides distansonis was associated with treatment response in both patient cohorts and preclinical models. The team also discovered that inhibiting IL-1R with an approved drug reduced intestinal inflammation without compromising treatment efficacy in pre-clinical models.
These findings highlight the potential of gut microbiota as biomarkers for toxicity and response to combined immune checkpoint blockade. Further research is needed to validate these biomarkers and investigate IL-1R inhibition as a potential therapeutic target for managing inflammation induced by immunotherapy. The study was supported by the Melanoma Moon Shot® and other foundations, underscoring the collaborative effort to advance cancer treatment.
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