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

1
Division of Nuclear Medicine, Department of Biomedical Imaging and Image-Guided Therapy, Medical University of Vienna, 1090 Vienna, Austria
2
Division of Hematology, Department of Medicine I, Medical University of Vienna, 1090 Vienna, Austria
*
Author to whom correspondence should be addressed.
Shared last authorship.
Academic Editors: Tomasz Mazurek, Aleksandra Gąsecka, Miłosz J. Jaguszewski and Piotr Zielenkiewicz
Biology 2021, 10(11), 1206; https://doi.org/10.3390/biology10111206
Received: 25 October 2021 / Revised: 16 November 2021 / Accepted: 17 November 2021 / Published: 19 November 2021
(This article belongs to the Special Issue The Etiology of Atherosclerosis/Coronary Artery Disease)
Immune checkpoint inhibitor (ICI) therapy has changed the management of many cancers endowed with poor prognosis. However, cardiotoxicity, as well as the possible progression of atherosclerosis, have been described. 2-[18F]fluorodeoxyglucose (FDG) positron emission tomography (PET) is a validated tool to quantify atherosclerotic inflammatory activity; therefore, we found it interesting to analyze the changes in maximum FDG standardized uptake values (SUVmax) and of target-to-background ratios (TBRs) in 117 arterial segments of 12 otherwise healthy, young lymphoma patients, underwent PET pre/post ICI treatment. As systemic immune activation surrogate markers, SUVmax of the bone marrow, spleen, and liver, as well high-sensitivity C-reactive protein (hsCRP) pre- and post-treatment, were additionally analyzed. ICI therapy induced arterial inflammatory activity, detected by increased TBR in all PET lesions. FDG uptake measured in other organs and hsCRP levels remained unchanged. Our findings show that cancer immunotherapy with ICI might be a critical moderator of atherosclerosis, with a possible subsequently increased risk of future cardiovascular events in oncological patients, even in young patients with low cardiovascular risk.
Background: 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. Methods: 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 (SUVmax) and target-to-background ratios (TBRs) were calculated along arterial segments. Additionally, metabolic activities (SUVmax) of the bone marrow, spleen, and liver were analyzed. The levels of high-sensitivity C-reactive protein (hsCRP) were assessed. Results: 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, p < 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, p < 0.001). FDG uptake measured in other organs and hsCRP levels remained unchanged after ICI therapy. Conclusions: 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. View Full-Text
Keywords: atherosclerosis; cardiovascular toxicity; cardio-oncology; immune checkpoint inhibitor; PET atherosclerosis; cardiovascular toxicity; cardio-oncology; immune checkpoint inhibitor; PET
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MDPI and ACS Style

Calabretta, R.; Staber, P.B.; Kornauth, C.; Lu, X.; Binder, P.; Pichler, V.; Mitterhauser, M.; Haug, A.; Li, X.; Hacker, M. Immune Checkpoint Inhibitor Therapy Induces Inflammatory Activity in the Large Arteries of Lymphoma Patients under 50 Years of Age. Biology 2021, 10, 1206. https://doi.org/10.3390/biology10111206

AMA Style

Calabretta R, Staber PB, Kornauth C, Lu X, Binder P, Pichler V, Mitterhauser M, Haug A, Li X, Hacker M. Immune Checkpoint Inhibitor Therapy Induces Inflammatory Activity in the Large Arteries of Lymphoma Patients under 50 Years of Age. Biology. 2021; 10(11):1206. https://doi.org/10.3390/biology10111206

Chicago/Turabian Style

Calabretta, Raffaella, Philipp B. Staber, Christoph Kornauth, Xia Lu, Patrick Binder, Verena Pichler, Markus Mitterhauser, Alexander Haug, Xiang Li, and Marcus Hacker. 2021. "Immune Checkpoint Inhibitor Therapy Induces Inflammatory Activity in the Large Arteries of Lymphoma Patients under 50 Years of Age" Biology 10, no. 11: 1206. https://doi.org/10.3390/biology10111206

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