20.500.12556/RUL-164829 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 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. gastrointestinal microbiome mRNA expression of PD-L1 and IFNγ immune checkpoint inhibitors metastatic melanoma predictive and prognostic biomarkers immune-related adverse events gastrointestinalni mikrobiom mRNA imunski kontrolni zaviralci metastatski melanom true false true Angleški jezik Slovenski jezik Članek v reviji 2024-11-13 12:08:45 2024-11-13 12:08:49 2024-11-22 14:56:18 0000-00-00 00:00:00 2023 0 0 14 str. iss. 7, art. 2016 Vol. 11 2023 0000-00-00 Zaloznikova Objavljeno apc 0000-00-00 0000-00-00 0000-00-00 616-006 2227-9059 10.3390/biomedicines11072016 159145219 biomedicines-11-02016.pdf biomedicines-11-02016.pdf 1 584A51FBACC571AE9D7FE7BA9FC6B2F2 7d03664f781795df20572605335dbb7e1582db7530c67b8639c8277e58913ac7 92cf57bc-a1af-11ef-b232-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=195589 https://www.mdpi.com/2227-9059/11/7/2016 1 4c5a7b7c-a1af-11ef-b232-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=195588 Medicinska fakulteta Biotehniška fakulteta 0 0 0