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Immune mediators as predictive biomarkers for anti-PD-1 antibody therapy in urothelial carcinoma

Introduction: This study aimed to identify immune mediators, including cytokines, chemokines, and growth factors, in the plasma for predicting treatment efficacy and immune-related adverse events (irAEs) in advanced urothelial carcinoma (aUC) treated with immune checkpoint inhibitors (ICIs). Methods...

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Autores principales: Shibata, Yosuke, Kishida, Takeshi, Kouro, Taku, Wei, Feifei, Igarashi, Yuka, Himuro, Hidetomo, Noguchi, Takeaki, Koizumi, Mitsuyuki, Suzuki, Takahisa, Osaka, Kimito, Saigusa, Yusuke, Sasada, Tetsuro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10679331/
https://www.ncbi.nlm.nih.gov/pubmed/38026978
http://dx.doi.org/10.3389/fphar.2023.1269935
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author Shibata, Yosuke
Kishida, Takeshi
Kouro, Taku
Wei, Feifei
Igarashi, Yuka
Himuro, Hidetomo
Noguchi, Takeaki
Koizumi, Mitsuyuki
Suzuki, Takahisa
Osaka, Kimito
Saigusa, Yusuke
Sasada, Tetsuro
author_facet Shibata, Yosuke
Kishida, Takeshi
Kouro, Taku
Wei, Feifei
Igarashi, Yuka
Himuro, Hidetomo
Noguchi, Takeaki
Koizumi, Mitsuyuki
Suzuki, Takahisa
Osaka, Kimito
Saigusa, Yusuke
Sasada, Tetsuro
author_sort Shibata, Yosuke
collection PubMed
description Introduction: This study aimed to identify immune mediators, including cytokines, chemokines, and growth factors, in the plasma for predicting treatment efficacy and immune-related adverse events (irAEs) in advanced urothelial carcinoma (aUC) treated with immune checkpoint inhibitors (ICIs). Methods: We enrolled 57 patients with aUC who were treated with the anti-programmed cell death protein 1 (PD-1) antibody pembrolizumab after the failure of platinum-based chemotherapy between February 2018 and December 2020. Plasma levels of 73 soluble immune mediators were measured before and 6 weeks after initiating pembrolizumab therapy. The association of estimated soluble immune mediators with clinical outcomes, including overall survival (OS), progression-free survival (PFS), anti-tumor responses, and irAEs, were statistically evaluated. Results: In the multivariate analysis, levels of 18 factors at baseline and 12 factors during treatment were significantly associated with OS. Regarding PFS, baseline levels of 17 factors were significantly associated with PFS. Higher levels of interleukin (IL)-6, IL-8, soluble tumor necrosis factor receptor 1 (sTNF-R1), and IL-12 (p40), both at baseline and post-treatment, were significantly associated with worse OS. Conversely, low IL-6 and high TWEAK levels at baseline were associated with irAEs. Among identified factors, interferon (IFN) γ and IL-12 (p40) were repeatedly identified; high baseline levels of these factors were risk factors for worse OS and PFS, as well as progressive disease. Notably, using correlation and principal component analysis, factors significantly associated with clinical outcomes were broadly classified into three groups exhibiting similar expression patterns. Discussion: Measuring plasma levels of soluble immune mediators, such as IL-6, IL-8, sTNF-R1, IFNγ, and IL-12 (p40), could be recommended for predicting prognosis and irAEs in ICI-treated patients with aUC.
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spelling pubmed-106793312023-11-13 Immune mediators as predictive biomarkers for anti-PD-1 antibody therapy in urothelial carcinoma Shibata, Yosuke Kishida, Takeshi Kouro, Taku Wei, Feifei Igarashi, Yuka Himuro, Hidetomo Noguchi, Takeaki Koizumi, Mitsuyuki Suzuki, Takahisa Osaka, Kimito Saigusa, Yusuke Sasada, Tetsuro Front Pharmacol Pharmacology Introduction: This study aimed to identify immune mediators, including cytokines, chemokines, and growth factors, in the plasma for predicting treatment efficacy and immune-related adverse events (irAEs) in advanced urothelial carcinoma (aUC) treated with immune checkpoint inhibitors (ICIs). Methods: We enrolled 57 patients with aUC who were treated with the anti-programmed cell death protein 1 (PD-1) antibody pembrolizumab after the failure of platinum-based chemotherapy between February 2018 and December 2020. Plasma levels of 73 soluble immune mediators were measured before and 6 weeks after initiating pembrolizumab therapy. The association of estimated soluble immune mediators with clinical outcomes, including overall survival (OS), progression-free survival (PFS), anti-tumor responses, and irAEs, were statistically evaluated. Results: In the multivariate analysis, levels of 18 factors at baseline and 12 factors during treatment were significantly associated with OS. Regarding PFS, baseline levels of 17 factors were significantly associated with PFS. Higher levels of interleukin (IL)-6, IL-8, soluble tumor necrosis factor receptor 1 (sTNF-R1), and IL-12 (p40), both at baseline and post-treatment, were significantly associated with worse OS. Conversely, low IL-6 and high TWEAK levels at baseline were associated with irAEs. Among identified factors, interferon (IFN) γ and IL-12 (p40) were repeatedly identified; high baseline levels of these factors were risk factors for worse OS and PFS, as well as progressive disease. Notably, using correlation and principal component analysis, factors significantly associated with clinical outcomes were broadly classified into three groups exhibiting similar expression patterns. Discussion: Measuring plasma levels of soluble immune mediators, such as IL-6, IL-8, sTNF-R1, IFNγ, and IL-12 (p40), could be recommended for predicting prognosis and irAEs in ICI-treated patients with aUC. Frontiers Media S.A. 2023-11-13 /pmc/articles/PMC10679331/ /pubmed/38026978 http://dx.doi.org/10.3389/fphar.2023.1269935 Text en Copyright © 2023 Shibata, Kishida, Kouro, Wei, Igarashi, Himuro, Noguchi, Koizumi, Suzuki, Osaka, Saigusa and Sasada. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Shibata, Yosuke
Kishida, Takeshi
Kouro, Taku
Wei, Feifei
Igarashi, Yuka
Himuro, Hidetomo
Noguchi, Takeaki
Koizumi, Mitsuyuki
Suzuki, Takahisa
Osaka, Kimito
Saigusa, Yusuke
Sasada, Tetsuro
Immune mediators as predictive biomarkers for anti-PD-1 antibody therapy in urothelial carcinoma
title Immune mediators as predictive biomarkers for anti-PD-1 antibody therapy in urothelial carcinoma
title_full Immune mediators as predictive biomarkers for anti-PD-1 antibody therapy in urothelial carcinoma
title_fullStr Immune mediators as predictive biomarkers for anti-PD-1 antibody therapy in urothelial carcinoma
title_full_unstemmed Immune mediators as predictive biomarkers for anti-PD-1 antibody therapy in urothelial carcinoma
title_short Immune mediators as predictive biomarkers for anti-PD-1 antibody therapy in urothelial carcinoma
title_sort immune mediators as predictive biomarkers for anti-pd-1 antibody therapy in urothelial carcinoma
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10679331/
https://www.ncbi.nlm.nih.gov/pubmed/38026978
http://dx.doi.org/10.3389/fphar.2023.1269935
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