The prognostic and predictive value of human gastrointestinal microbiome and exosomal mRNA expression of PD-L1 and IFNγ for immune checkpoint inhibitors response in metastatic melanoma patients : protocol trial

Erman, Ana (author), Ignjatović, Marija (author), Leskovšek, Katja (author), Miceska, Simona (author), Lampreht Tratar, Urša (author), Omerzel, Maša (author), Kloboves-Prevodnik, Veronika (author), Čemažar, Maja (author), Kandolf Sekulović, Lidija (author), Avguštin, Gorazd (author), Ocvirk, Janja (author), Mesti, Tanja (author)

Background: Immunotherapy has been successful in treating advanced melanoma, but a large proportion of patients do not respond to the treatment with immune checkpoint inhibitors (ICIs). Preclinical and small cohort studies suggest gastrointestinal microbiome composition and exosomal mRNA expression of PD-L1 and IFNγ from the primary tumor, stool and body fluids as potential biomarkers for response. Methods: Patients treated with immune checkpoint inhibitors as a first line treatment for metastatic melanoma are recruted to this prospective study. Stool samples are submitted before the start of treatment, at the 12th (+/−2) week and 28th (+/−2) week, and at the occurrence of event (suspected disease progression/hyperprogression, immune-related adverse event (irAE), deterioration). Peripheral venous blood samples are taken additionally at the same time points for cytologic and molecular tests. Histological material from the tumor tissue is obtained before the start of immunotherapy treatment. Primary objectives are to determine whether the human gastrointestinal microbiome (bacterial and viral) and the exosomal mRNA expression of PD-L1 and IFNγ and its dynamics predicts the response to treatment with PD-1 and CTLA-4 inhibitors and its association with the occurrence of irAE. The response is evaluated radiologically with imaging methods in accordance with the irRECIST criteria. Conclusions: This is the first study to combine and investigate multiple potential predictive and prognostic biomarkers and their dynamics in first line ICI in metastatic melanoma patients.

• Language: English
• Keywords: gastrointestinal microbiome, mRNA expression of PD-L1 and IFNγ, immune checkpoint inhibitors, metastatic melanoma, predictive and prognostic biomarkers, immune-related adverse events
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: MF - Faculty of Medicine; BF - Biotechnical Faculty
• Publication status: Published
• Publication version: Version of Record
• Year: 2023
• Number of pages: 14 str.
• Numbering: Vol. 11, iss. 7, art. 2016
• PID: 20.500.12556/RUL-164829
• UDC: 616-006
• ISSN on article: 2227-9059
• DOI: 10.3390/biomedicines11072016
• COBISS.SI-ID: 159145219
• Publication date in RUL: 13.11.2024

Record is a part of a journal

• Title: Biomedicines
• Shortened title: Biomedicines
• Publisher: MDPI
• ISSN: 2227-9059
• COBISS.SI-ID: 523006745

Licences

• License: CC BY 4.0, Creative Commons Attribution 4.0 International
• Link: http://creativecommons.org/licenses/by/4.0/
• Description: This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.

Secondary language

• Language: Slovenian
• Keywords: gastrointestinalni mikrobiom, mRNA, imunski kontrolni zaviralci, metastatski melanom

Projects

• Funder: ARRS - Slovenian Research Agency
• Project number: P3-0321
• Name: Napovedni dejavniki poteka bolezni in odgovora na zdravljenje pri različnih vrstah raka