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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...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10377397/ https://www.ncbi.nlm.nih.gov/pubmed/37509655 http://dx.doi.org/10.3390/biomedicines11072016 |
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author | Erman, Ana Ignjatović, Marija Leskovšek, Katja Miceska, Simona Lampreht Tratar, Urša Bošnjak, Maša Kloboves Prevodnik, Veronika Čemažar, Maja Kandolf Sekulovič, Lidija Avguštin, Gorazd Ocvirk, Janja Mesti, Tanja |
author_facet | Erman, Ana Ignjatović, Marija Leskovšek, Katja Miceska, Simona Lampreht Tratar, Urša Bošnjak, Maša Kloboves Prevodnik, Veronika Čemažar, Maja Kandolf Sekulovič, Lidija Avguštin, Gorazd Ocvirk, Janja Mesti, Tanja |
author_sort | Erman, Ana |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-10377397 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-103773972023-07-29 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 Ignjatović, Marija Leskovšek, Katja Miceska, Simona Lampreht Tratar, Urša Bošnjak, Maša Kloboves Prevodnik, Veronika Čemažar, Maja Kandolf Sekulovič, Lidija Avguštin, Gorazd Ocvirk, Janja Mesti, Tanja Biomedicines Study Protocol 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. MDPI 2023-07-18 /pmc/articles/PMC10377397/ /pubmed/37509655 http://dx.doi.org/10.3390/biomedicines11072016 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Study Protocol Erman, Ana Ignjatović, Marija Leskovšek, Katja Miceska, Simona Lampreht Tratar, Urša Bošnjak, Maša Kloboves Prevodnik, Veronika Čemažar, Maja Kandolf Sekulovič, Lidija Avguštin, Gorazd Ocvirk, Janja Mesti, Tanja 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 |
title | 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 |
title_full | 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 |
title_fullStr | 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 |
title_full_unstemmed | 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 |
title_short | 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 |
title_sort | 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 |
topic | Study Protocol |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10377397/ https://www.ncbi.nlm.nih.gov/pubmed/37509655 http://dx.doi.org/10.3390/biomedicines11072016 |
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