Immune Checkpoint Inhibitor Therapy Induces Inflammatory Activity in the Large Arteries of Lymphoma Patients under 50 Years of Age

<b>Background:</b> Immune checkpoint inhibitors (ICI) have transformed the management of various cancers. Serious and potentially fatal cardiovascular toxicity, as well as a progression of atherosclerosis, have been described, mainly in elderly and comorbid patients. <b>Methods:<...

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Autores principales:	Raffaella Calabretta, Philipp B. Staber, Christoph Kornauth, Xia Lu, Patrick Binder, Verena Pichler, Markus Mitterhauser, Alexander Haug, Xiang Li, Marcus Hacker
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	atherosclerosis cardiovascular toxicity cardio-oncology immune checkpoint inhibitor PET Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/ee9c387c93ac4977888f8379e73ab6a8
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spelling	oai:doaj.org-article:ee9c387c93ac4977888f8379e73ab6a82021-11-25T16:48:04ZImmune Checkpoint Inhibitor Therapy Induces Inflammatory Activity in the Large Arteries of Lymphoma Patients under 50 Years of Age10.3390/biology101112062079-7737https://doaj.org/article/ee9c387c93ac4977888f8379e73ab6a82021-11-01T00:00:00Zhttps://www.mdpi.com/2079-7737/10/11/1206https://doaj.org/toc/2079-7737<b>Background:</b> Immune checkpoint inhibitors (ICI) have transformed the management of various cancers. Serious and potentially fatal cardiovascular toxicity, as well as a progression of atherosclerosis, have been described, mainly in elderly and comorbid patients. <b>Methods:</b> We investigated 117 arterial segments of 12 young (under 50 years of age), otherwise healthy lymphoma patients pre/post-ICI treatment using 2-[18F]fluorodeoxyglucose (FDG) positron emission tomography (PET). Maximum FDG standardized uptake values (SUV<sub>max</sub>) and target-to-background ratios (TBRs) were calculated along arterial segments. Additionally, metabolic activities (SUV<sub>max</sub>) of the bone marrow, spleen, and liver were analyzed. The levels of high-sensitivity C-reactive protein (hsCRP) were assessed. <b>Results:</b> ICI therapy induced arterial inflammatory activity, detected by increased TBR in arterial segments without pre-existing inflammation (TBRneg_pre = 1.20 ± 0.22 vs. TBRneg_post = 1.71 ± 0.45, <i>p</i> < 0.001), whereas already-inflamed lesions remained unchanged. Dormant calcified segments (Hounsfield Units-HU ≥ 130) showed a significant increase in TBR values after ICI treatment (TBRcalc_pre = 1.36 ± 0.38 vs. TBRcalc_post = 1.76 ± 0.42, <i>p</i> < 0.001). FDG uptake measured in other organs and hsCRP levels remained unchanged after ICI therapy. <b>Conclusions:</b> Although the effects of ICI therapy on arterial inflammation are still incompletely understood, cancer immunotherapy might be a critical moderator of atherosclerosis with a subsequently increased risk of future cerebro- and/or cardiovascular events in young oncological patients.Raffaella CalabrettaPhilipp B. StaberChristoph KornauthXia LuPatrick BinderVerena PichlerMarkus MitterhauserAlexander HaugXiang LiMarcus HackerMDPI AGarticleatherosclerosiscardiovascular toxicitycardio-oncologyimmune checkpoint inhibitorPETBiology (General)QH301-705.5ENBiology, Vol 10, Iss 1206, p 1206 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	atherosclerosis cardiovascular toxicity cardio-oncology immune checkpoint inhibitor PET Biology (General) QH301-705.5
spellingShingle	atherosclerosis cardiovascular toxicity cardio-oncology immune checkpoint inhibitor PET Biology (General) QH301-705.5 Raffaella Calabretta Philipp B. Staber Christoph Kornauth Xia Lu Patrick Binder Verena Pichler Markus Mitterhauser Alexander Haug Xiang Li Marcus Hacker Immune Checkpoint Inhibitor Therapy Induces Inflammatory Activity in the Large Arteries of Lymphoma Patients under 50 Years of Age
description	<b>Background:</b> Immune checkpoint inhibitors (ICI) have transformed the management of various cancers. Serious and potentially fatal cardiovascular toxicity, as well as a progression of atherosclerosis, have been described, mainly in elderly and comorbid patients. <b>Methods:</b> We investigated 117 arterial segments of 12 young (under 50 years of age), otherwise healthy lymphoma patients pre/post-ICI treatment using 2-[18F]fluorodeoxyglucose (FDG) positron emission tomography (PET). Maximum FDG standardized uptake values (SUV<sub>max</sub>) and target-to-background ratios (TBRs) were calculated along arterial segments. Additionally, metabolic activities (SUV<sub>max</sub>) of the bone marrow, spleen, and liver were analyzed. The levels of high-sensitivity C-reactive protein (hsCRP) were assessed. <b>Results:</b> ICI therapy induced arterial inflammatory activity, detected by increased TBR in arterial segments without pre-existing inflammation (TBRneg_pre = 1.20 ± 0.22 vs. TBRneg_post = 1.71 ± 0.45, <i>p</i> < 0.001), whereas already-inflamed lesions remained unchanged. Dormant calcified segments (Hounsfield Units-HU ≥ 130) showed a significant increase in TBR values after ICI treatment (TBRcalc_pre = 1.36 ± 0.38 vs. TBRcalc_post = 1.76 ± 0.42, <i>p</i> < 0.001). FDG uptake measured in other organs and hsCRP levels remained unchanged after ICI therapy. <b>Conclusions:</b> Although the effects of ICI therapy on arterial inflammation are still incompletely understood, cancer immunotherapy might be a critical moderator of atherosclerosis with a subsequently increased risk of future cerebro- and/or cardiovascular events in young oncological patients.
format	article
author	Raffaella Calabretta Philipp B. Staber Christoph Kornauth Xia Lu Patrick Binder Verena Pichler Markus Mitterhauser Alexander Haug Xiang Li Marcus Hacker
author_facet	Raffaella Calabretta Philipp B. Staber Christoph Kornauth Xia Lu Patrick Binder Verena Pichler Markus Mitterhauser Alexander Haug Xiang Li Marcus Hacker
author_sort	Raffaella Calabretta
title	Immune Checkpoint Inhibitor Therapy Induces Inflammatory Activity in the Large Arteries of Lymphoma Patients under 50 Years of Age
title_short	Immune Checkpoint Inhibitor Therapy Induces Inflammatory Activity in the Large Arteries of Lymphoma Patients under 50 Years of Age
title_full	Immune Checkpoint Inhibitor Therapy Induces Inflammatory Activity in the Large Arteries of Lymphoma Patients under 50 Years of Age
title_fullStr	Immune Checkpoint Inhibitor Therapy Induces Inflammatory Activity in the Large Arteries of Lymphoma Patients under 50 Years of Age
title_full_unstemmed	Immune Checkpoint Inhibitor Therapy Induces Inflammatory Activity in the Large Arteries of Lymphoma Patients under 50 Years of Age
title_sort	immune checkpoint inhibitor therapy induces inflammatory activity in the large arteries of lymphoma patients under 50 years of age
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/ee9c387c93ac4977888f8379e73ab6a8
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Immune Checkpoint Inhibitor Therapy Induces Inflammatory Activity in the Large Arteries of Lymphoma Patients under 50 Years of Age

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