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FGF/FGFR genomic amplification as a predictive biomarker for immune checkpoint blockade resistance: a short report

A novel crosstalk between immunogenic and oncometabolic pathways triggered by T cell-released interferon-gamma (IFN-ɣ) has been recently identified. This IFN-ɣ-pyruvate kinase M2-β-catenin axis relies on fibroblast growth factor 2 (FGF2) signaling in tumor cells and leads to hyperprogressive disease...

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Autores principales: Roussot, Nicolas, Lecuelle, Julie, Dalens, Lorraine, Truntzer, Caroline, Ghiringhelli, Francois
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BMJ Publishing Group 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10618988/
https://www.ncbi.nlm.nih.gov/pubmed/37890888
http://dx.doi.org/10.1136/jitc-2023-007763
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author Roussot, Nicolas
Lecuelle, Julie
Dalens, Lorraine
Truntzer, Caroline
Ghiringhelli, Francois
author_facet Roussot, Nicolas
Lecuelle, Julie
Dalens, Lorraine
Truntzer, Caroline
Ghiringhelli, Francois
author_sort Roussot, Nicolas
collection PubMed
description A novel crosstalk between immunogenic and oncometabolic pathways triggered by T cell-released interferon-gamma (IFN-ɣ) has been recently identified. This IFN-ɣ-pyruvate kinase M2-β-catenin axis relies on fibroblast growth factor 2 (FGF2) signaling in tumor cells and leads to hyperprogressive disease on immune checkpoint blockade (ICB) in preclinical models. This result underlines how IFN-ɣ signaling may have distinct effects on tumor cells depending on their oncogenic and metabolic features. On the basis of these data, this study aims to explore the relationship between genomic tumor FGF2 or FGF/FGF receptor (FGFR) amplification and immunotherapy response in patients with metastatic solid cancers. We used a large genomic data set of 545 ICB-treated patients and compared outcomes between those with and without FGF2 genomic amplification. Patients with no FGF2 genomic amplification had significantly longer progression-free survival (PFS) (HR=0.55 (95% CI 0.4, 0.8); p value=0.005) and overall survival (OS) (HR=0.56 (0.3, 0.9); p value=0.02) than patients harboring an FGF2 amplification. We next questioned whether such an observation may extend to genomic amplification of the FGF/FGFR pathway. Similarly, patients with no FGF/FGFR genomic amplification had longer PFS (HR=0.71 (0.8, 0.9), p value=0.004) and OS (HR=0.77 (0.6, 1); p value=0.06). RNA sequencing analysis of tumors between the amplified and non-amplified populations showed distinct expression profiles concerning oncogenic pathways. Importantly, using a cohort of patients untreated with ICB from the The Cancer Genome Atlas, we show that FGF2 and FGF/FGFR genomic amplification were not associated with prognosis, thus demonstrating that we identified a predictive biomarker of immunotherapy resistance.
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spelling pubmed-106189882023-11-02 FGF/FGFR genomic amplification as a predictive biomarker for immune checkpoint blockade resistance: a short report Roussot, Nicolas Lecuelle, Julie Dalens, Lorraine Truntzer, Caroline Ghiringhelli, Francois J Immunother Cancer Immunotherapy Biomarkers A novel crosstalk between immunogenic and oncometabolic pathways triggered by T cell-released interferon-gamma (IFN-ɣ) has been recently identified. This IFN-ɣ-pyruvate kinase M2-β-catenin axis relies on fibroblast growth factor 2 (FGF2) signaling in tumor cells and leads to hyperprogressive disease on immune checkpoint blockade (ICB) in preclinical models. This result underlines how IFN-ɣ signaling may have distinct effects on tumor cells depending on their oncogenic and metabolic features. On the basis of these data, this study aims to explore the relationship between genomic tumor FGF2 or FGF/FGF receptor (FGFR) amplification and immunotherapy response in patients with metastatic solid cancers. We used a large genomic data set of 545 ICB-treated patients and compared outcomes between those with and without FGF2 genomic amplification. Patients with no FGF2 genomic amplification had significantly longer progression-free survival (PFS) (HR=0.55 (95% CI 0.4, 0.8); p value=0.005) and overall survival (OS) (HR=0.56 (0.3, 0.9); p value=0.02) than patients harboring an FGF2 amplification. We next questioned whether such an observation may extend to genomic amplification of the FGF/FGFR pathway. Similarly, patients with no FGF/FGFR genomic amplification had longer PFS (HR=0.71 (0.8, 0.9), p value=0.004) and OS (HR=0.77 (0.6, 1); p value=0.06). RNA sequencing analysis of tumors between the amplified and non-amplified populations showed distinct expression profiles concerning oncogenic pathways. Importantly, using a cohort of patients untreated with ICB from the The Cancer Genome Atlas, we show that FGF2 and FGF/FGFR genomic amplification were not associated with prognosis, thus demonstrating that we identified a predictive biomarker of immunotherapy resistance. BMJ Publishing Group 2023-10-27 /pmc/articles/PMC10618988/ /pubmed/37890888 http://dx.doi.org/10.1136/jitc-2023-007763 Text en © Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. https://creativecommons.org/licenses/by-nc/4.0/This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) .
spellingShingle Immunotherapy Biomarkers
Roussot, Nicolas
Lecuelle, Julie
Dalens, Lorraine
Truntzer, Caroline
Ghiringhelli, Francois
FGF/FGFR genomic amplification as a predictive biomarker for immune checkpoint blockade resistance: a short report
title FGF/FGFR genomic amplification as a predictive biomarker for immune checkpoint blockade resistance: a short report
title_full FGF/FGFR genomic amplification as a predictive biomarker for immune checkpoint blockade resistance: a short report
title_fullStr FGF/FGFR genomic amplification as a predictive biomarker for immune checkpoint blockade resistance: a short report
title_full_unstemmed FGF/FGFR genomic amplification as a predictive biomarker for immune checkpoint blockade resistance: a short report
title_short FGF/FGFR genomic amplification as a predictive biomarker for immune checkpoint blockade resistance: a short report
title_sort fgf/fgfr genomic amplification as a predictive biomarker for immune checkpoint blockade resistance: a short report
topic Immunotherapy Biomarkers
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10618988/
https://www.ncbi.nlm.nih.gov/pubmed/37890888
http://dx.doi.org/10.1136/jitc-2023-007763
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