Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Filippova, T.
Characterization of the gut and skin microbiota in melanoma patients treated with immune checkpoint inhibitors: pilot study
Humanmedizin; [ Diplomarbeit ] Medizinische Universität Graz; 2023. pp. 58
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- Autor*innen der Med Uni Graz:
- Betreuer*innen:
- Rainer Barbara
- Richtig Erika
- Altmetrics:
- Abstract:
- Introduction: Recent studies have shown that the gut microbiota can affect the efficacy of palliative immune checkpoint inhibitor (ICI) therapy in patients with advanced melanoma. In a realworld setting, we aimed to investigate (1) changes of the oral, skin and gut microbiota in response to adjuvant and palliative ICIs in melanoma patients, (2) differences in composition of the gut microbiota between responders versus non-responders to ICIs, and (3) alterations of the gut microbiota of patients with severe treatment-related adverse events (trAEs). Methods: This prospective cohort study included patients A) with recently diagnosed melanoma (stages III/IV) receiving adjuvant/palliative ICI therapy, and B) in complete remission after adjuvant/palliative ICI therapy (stages III/IV). Skin, oral and stool samples were collected before and 12 weeks after ICI initiation (cohort A), and at routine follow-up exam (cohort B). Patient-reported questionnaires on nutrition and itch were collected at similar time points. 16SrRNA gene sequencing was used to perform diversity and taxonomic characterization of the microbiome. Wilcoxon signed-rank tests and t-tests were used to compare microbial diversity and abundance over time. Results: In cohort A, bacterial diversity of oral and gut microbiota was comparable before and 12 weeks after start of ICI therapy. The skin microbiota composition changed during ICI therapy, and Campylobacter and Faecalibacterium were significantly more abundant 12 weeks after initiation of therapy. Several bacterial taxa of the gut microbiota (Parabacteroides (Tannerellaceae), Odoribacter (Marinifilaceae) and Alphaproteobacteria) were associated with therapy response. Non-responders (cohort A) had significantly more Enterococcaceae and Faecalitalea in their gut microbiome than patients from cohort B (long-term remission), which had more Dorea. Patients with highgrade trAE (≥grade 3) had significantly more Barnesiellaceae, Rikenellaceae, Parasutterella, and Ruminococcaceae NK4A214 in their intestinal microbiome. Conclusion: These findings could help to identify new biomarkers to predict or even improve the response to ICI therapy and prevent severe side effects. For the first time, changes in the skin microbiome during ICI therapy have been described. Further research is needed to understand the role of gut and skin microbiota and their importance in the development of trAEs.