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Serological biomarkers predict immune-related adverse events and clinical benefit in patients with advanced gastrointestinal cancers
BACKGROUND: Immune checkpoint inhibitors (ICIs) have dramatically improved survival in advanced gastrointestinal (GI) cancer patients, but also resulted in immune-related adverse events (irAEs). This study aimed to evaluate serological biomarkers of irAEs and treatment response in GI cancer patients...
Autores principales: | , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9492966/ https://www.ncbi.nlm.nih.gov/pubmed/36159840 http://dx.doi.org/10.3389/fimmu.2022.987568 |
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author | Wang, Yanni Zou, Jianling Li, Yun Jiao, Xi Wang, Yujiao Zhuo, Na Gao, Mengting Gong, Jifang Li, Jian Zhang, Xiaotian Wang, Xicheng Peng, Zhi Qi, Changsong Wang, Zhenghang Li, Jie Li, Yan Shen, Lin Zhang, Henghui Lu, Zhihao |
author_facet | Wang, Yanni Zou, Jianling Li, Yun Jiao, Xi Wang, Yujiao Zhuo, Na Gao, Mengting Gong, Jifang Li, Jian Zhang, Xiaotian Wang, Xicheng Peng, Zhi Qi, Changsong Wang, Zhenghang Li, Jie Li, Yan Shen, Lin Zhang, Henghui Lu, Zhihao |
author_sort | Wang, Yanni |
collection | PubMed |
description | BACKGROUND: Immune checkpoint inhibitors (ICIs) have dramatically improved survival in advanced gastrointestinal (GI) cancer patients, but also resulted in immune-related adverse events (irAEs). This study aimed to evaluate serological biomarkers of irAEs and treatment response in GI cancer patients. PATIENTS AND METHODS: Metastatic GI cancer patients were enrolled between August 1, 2015, and July 31, 2017. Serum samples were collected at baseline, and a panel of 59 serum biomarkers was tested. The occurrence of irAEs was analyzed, and serological biomarker expression was correlated with irAE incidence and prognosis. RESULTS: Fifty-one patients were enrolled, of whom 47.1% (24/51) were diagnosed with irAEs, including 4 patients (7.8%) with grade 3-5 irAEs. The most common irAE was thyroiditis (9/51, 17.6%), followed by colitis (7/51, 13.7%). The expression of CD28 (P = 0.042), IL-4 (P = 0.033), IL-15 (P = 0.024) and PD-L1 (P = 0.018) was significantly elevated in patients with grade 3-5 irAEs. For organ-specific irAEs, IL-6 levels were higher in patients with thyroiditis and colitis, while IL-22 and SCF levels were higher in patients with colitis. Increased IL-1α, IL-21, LIF, and PIGF-1 levels were significantly associated with myositis incidence, while the serum levels of six cytokines (BTLA, GM-CSF, IL-4, PD-1, PD-L1 and TIM-3) were higher in patients with rash. Prognostic analysis showed that patients with irAEs had better tumor response (P = 0.029), improved PFS (median survival: undefined vs. 2.1 months, P = 0.002), and extended OS (median survival: undefined vs. 4.3 months, P = 0.003). The prognostic value of irAEs was only significant in patients who received anti-PD-1 inhibitors, but not in those who received anti-PD-L1 inhibitors. Besides, elevated BTLA (median OS: not reached vs. 7 months; P = 0.0168) and PD-1 (median OS: not reached vs. 7 months; P = 0.0223) concentrations were associated with longer OS. CONCLUSIONS: Serological proteins are promising markers for predicting immune-related toxicity and prognosis in GI cancer patients. Organ-specific irAEs have various cytokine profiles. Although further validation is needed before clinical application, this study provided a direction for identifying patients at risk for irAEs, and guiding patient selection for ICI therapy. |
format | Online Article Text |
id | pubmed-9492966 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-94929662022-09-23 Serological biomarkers predict immune-related adverse events and clinical benefit in patients with advanced gastrointestinal cancers Wang, Yanni Zou, Jianling Li, Yun Jiao, Xi Wang, Yujiao Zhuo, Na Gao, Mengting Gong, Jifang Li, Jian Zhang, Xiaotian Wang, Xicheng Peng, Zhi Qi, Changsong Wang, Zhenghang Li, Jie Li, Yan Shen, Lin Zhang, Henghui Lu, Zhihao Front Immunol Immunology BACKGROUND: Immune checkpoint inhibitors (ICIs) have dramatically improved survival in advanced gastrointestinal (GI) cancer patients, but also resulted in immune-related adverse events (irAEs). This study aimed to evaluate serological biomarkers of irAEs and treatment response in GI cancer patients. PATIENTS AND METHODS: Metastatic GI cancer patients were enrolled between August 1, 2015, and July 31, 2017. Serum samples were collected at baseline, and a panel of 59 serum biomarkers was tested. The occurrence of irAEs was analyzed, and serological biomarker expression was correlated with irAE incidence and prognosis. RESULTS: Fifty-one patients were enrolled, of whom 47.1% (24/51) were diagnosed with irAEs, including 4 patients (7.8%) with grade 3-5 irAEs. The most common irAE was thyroiditis (9/51, 17.6%), followed by colitis (7/51, 13.7%). The expression of CD28 (P = 0.042), IL-4 (P = 0.033), IL-15 (P = 0.024) and PD-L1 (P = 0.018) was significantly elevated in patients with grade 3-5 irAEs. For organ-specific irAEs, IL-6 levels were higher in patients with thyroiditis and colitis, while IL-22 and SCF levels were higher in patients with colitis. Increased IL-1α, IL-21, LIF, and PIGF-1 levels were significantly associated with myositis incidence, while the serum levels of six cytokines (BTLA, GM-CSF, IL-4, PD-1, PD-L1 and TIM-3) were higher in patients with rash. Prognostic analysis showed that patients with irAEs had better tumor response (P = 0.029), improved PFS (median survival: undefined vs. 2.1 months, P = 0.002), and extended OS (median survival: undefined vs. 4.3 months, P = 0.003). The prognostic value of irAEs was only significant in patients who received anti-PD-1 inhibitors, but not in those who received anti-PD-L1 inhibitors. Besides, elevated BTLA (median OS: not reached vs. 7 months; P = 0.0168) and PD-1 (median OS: not reached vs. 7 months; P = 0.0223) concentrations were associated with longer OS. CONCLUSIONS: Serological proteins are promising markers for predicting immune-related toxicity and prognosis in GI cancer patients. Organ-specific irAEs have various cytokine profiles. Although further validation is needed before clinical application, this study provided a direction for identifying patients at risk for irAEs, and guiding patient selection for ICI therapy. Frontiers Media S.A. 2022-09-08 /pmc/articles/PMC9492966/ /pubmed/36159840 http://dx.doi.org/10.3389/fimmu.2022.987568 Text en Copyright © 2022 Wang, Zou, Li, Jiao, Wang, Zhuo, Gao, Gong, Li, Zhang, Wang, Peng, Qi, Wang, Li, Li, Shen, Zhang and Lu 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 | Immunology Wang, Yanni Zou, Jianling Li, Yun Jiao, Xi Wang, Yujiao Zhuo, Na Gao, Mengting Gong, Jifang Li, Jian Zhang, Xiaotian Wang, Xicheng Peng, Zhi Qi, Changsong Wang, Zhenghang Li, Jie Li, Yan Shen, Lin Zhang, Henghui Lu, Zhihao Serological biomarkers predict immune-related adverse events and clinical benefit in patients with advanced gastrointestinal cancers |
title | Serological biomarkers predict immune-related adverse events and clinical benefit in patients with advanced gastrointestinal cancers |
title_full | Serological biomarkers predict immune-related adverse events and clinical benefit in patients with advanced gastrointestinal cancers |
title_fullStr | Serological biomarkers predict immune-related adverse events and clinical benefit in patients with advanced gastrointestinal cancers |
title_full_unstemmed | Serological biomarkers predict immune-related adverse events and clinical benefit in patients with advanced gastrointestinal cancers |
title_short | Serological biomarkers predict immune-related adverse events and clinical benefit in patients with advanced gastrointestinal cancers |
title_sort | serological biomarkers predict immune-related adverse events and clinical benefit in patients with advanced gastrointestinal cancers |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9492966/ https://www.ncbi.nlm.nih.gov/pubmed/36159840 http://dx.doi.org/10.3389/fimmu.2022.987568 |
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