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Emerging Role of Immunotherapies in Cancer and Their Cardiotoxic Effects
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Emerging Role of Immunotherapies in Cancer and Their Cardiotoxic Effects

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Oncology".

Deadline for manuscript submissions: closed (31 January 2022) | Viewed by 8633

Special Issue Editors

Prof. Dr. Tienush Rassaf

E-Mail Website
Guest Editor
West German Heart and Vascular Center, Department of Cardiology and Vascular Medicine, University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany
Interests: cardioprotection; heart failure; cardio-oncology; myocardial infarction; nitrite and nitric oxide signalling
Dr. Lars Michel

E-Mail Website
Guest Editor
West German Heart and Vascular Center, Department of Cardiology and Vascular Medicine, University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany
Interests: biomarkers; cardio-immunology; cardioprotection; cardio-oncology; myocardial infarction

Special Issue Information

Dear Colleagues,

Immune checkpoint inhibition (ICI) and chimeric antigen receptor (CAR) T cell therapy are emerging immunotherapies in cancer and have improved the survival of cancer patients in recent years across various types of cancer. Adjuvant and neoadjuvant study concepts using both therapies are under development. However, both therapies cause a wide range of immune-related adverse events (irAEs), including incompletely characterized forms of cardiotoxicity. In the light of the rapidly growing number of patients receiving such therapies, there is an indispensable need to identify mechanisms of cardiotoxicity in order to prevent, reduce, and protect from such toxic effects.

We, therefore, invite investigators to contribute original research as well as review articles that focus on efforts to understand and elucidate various aspects of the mechanisms of cardiotoxicity in cancer immunotherapy, including molecular, genetic/epigenetic, and immunological findings.

Prof. Dr. Tienush Rassaf
Dr. Lars Michel
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • cardiotoxicity
  • immune checkpoint inhibitors
  • CAR T cells
  • cardio-oncology
  • myocarditis
  • heart failure
  • cancer
  • cancer therapy

Published Papers (3 papers)

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Research

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12 pages, 7197 KiB  
Article
PD1 Deficiency Modifies Cardiac Immunity during Baseline Conditions and in Reperfused Acute Myocardial Infarction
by Lars Michel, Sebastian Korste, Armin Spomer, Ulrike Barbara Hendgen-Cotta, Tienush Rassaf and Matthias Totzeck
Int. J. Mol. Sci. 2022, 23(14), 7533; https://doi.org/10.3390/ijms23147533 - 07 Jul 2022
Cited by 5 | Viewed by 2012
Abstract
The programmed cell death protein 1 (PD1) immune checkpoint prevents inflammatory tissue damage by inhibiting immune reactions. Understanding the relevance of cardiac PD1 signaling may provide new insights into the inflammatory events under baseline conditions and disease. Here, we demonstrate distinct immunological changes [...] Read more.
The programmed cell death protein 1 (PD1) immune checkpoint prevents inflammatory tissue damage by inhibiting immune reactions. Understanding the relevance of cardiac PD1 signaling may provide new insights into the inflammatory events under baseline conditions and disease. Here, we demonstrate distinct immunological changes upon PD1 deficiency in healthy hearts and during reperfused acute myocardial infarction (repAMI). In PD1-deficient mice, upregulated inflammatory cytokines were identified under baseline conditions including cardiac interleukins and extracellular signal-related kinase 1/2 (ERK1/2). A murine in vivo repAMI model to determine inflammatory changes in the early phase showed downregulation of the ligand PDL1, paralleled by an endothelial injury, indicated by loss of the CD31 signal. Immunofluorescence imaging showed decreased PDL1 expression specifically in the infarct zone, highlighting an involvement in PDL1 in myocardial injury response. Pharmacological depletion of PD1 prior to repAMI did not alter the area of infarction but led to increased numbers of CD8+ T cells in treated mice. We conclude that PD1/PDL1 signaling plays a significant role in healthy hearts and repAMI, emphasizing the relevance of adaptive immunity during myocardial injury. The findings highlight the risk for adverse outcomes from acute myocardial infarction in the growing group of patients receiving immune checkpoint inhibitor therapy. Full article
(This article belongs to the Special Issue Emerging Role of Immunotherapies in Cancer and Their Cardiotoxic Effects)
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Review

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23 pages, 8719 KiB  
Review
Shining Damaged Hearts: Immunotherapy-Related Cardiotoxicity in the Spotlight of Nuclear Cardiology
by David Kersting, Stephan Settelmeier, Ilektra-Antonia Mavroeidi, Ken Herrmann, Robert Seifert and Christoph Rischpler
Int. J. Mol. Sci. 2022, 23(7), 3802; https://doi.org/10.3390/ijms23073802 - 30 Mar 2022
Cited by 3 | Viewed by 2070
Abstract
The emerging use of immunotherapies in cancer treatment increases the risk of immunotherapy-related cardiotoxicity. In contrast to conventional chemotherapy, these novel therapies have expanded the forms and presentations of cardiovascular damage to a broad spectrum from asymptomatic changes to fulminant short- and long-term [...] Read more.
The emerging use of immunotherapies in cancer treatment increases the risk of immunotherapy-related cardiotoxicity. In contrast to conventional chemotherapy, these novel therapies have expanded the forms and presentations of cardiovascular damage to a broad spectrum from asymptomatic changes to fulminant short- and long-term complications in terms of cardiomyopathy, arrythmia, and vascular disease. In cancer patients and, particularly, cancer patients undergoing (immune-)therapy, cardio-oncological monitoring is a complex interplay between pretherapeutic risk assessment, identification of impending cardiotoxicity, and post-therapeutic surveillance. For these purposes, the cardio-oncologist can revert to a broad spectrum of nuclear cardiological diagnostic workup. The most promising commonly used nuclear medicine imaging techniques in relation to immunotherapy will be discussed in this review article with a special focus on the continuous development of highly specific molecular markers and steadily improving methods of image generation. The review closes with an outlook on possible new developments of molecular imaging and advanced image evaluation techniques in this exciting and increasingly growing field of immunotherapy-related cardiotoxicity. Full article
(This article belongs to the Special Issue Emerging Role of Immunotherapies in Cancer and Their Cardiotoxic Effects)
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14 pages, 1065 KiB  
Review
Potential Role of Neutrophil Extracellular Traps in Cardio-Oncology
by Kai-Hung Cheng, Gregory P. Contreras and Ting-Yu Yeh
Int. J. Mol. Sci. 2022, 23(7), 3573; https://doi.org/10.3390/ijms23073573 - 25 Mar 2022
Cited by 3 | Viewed by 3878
Abstract
Cardiovascular toxicity has emerged as the leading cause of death in patients undergoing cancer treatment. Thus, cardio-oncology (CO) care must also focus on the prevention and management of related cardiovascular (CV) complications caused by cancer therapy. Neutrophil extracellular traps (NETs)—entities with released DNA, [...] Read more.
Cardiovascular toxicity has emerged as the leading cause of death in patients undergoing cancer treatment. Thus, cardio-oncology (CO) care must also focus on the prevention and management of related cardiovascular (CV) complications caused by cancer therapy. Neutrophil extracellular traps (NETs)—entities with released DNA, proteases, proinflammatory and prooxidative substances from blasted neutrophils—play an important role in cancer proliferation, propagation metastasis, and incident CV events (acute coronary syndrome, thromboembolic events, and heart failure). Although NETs have been shown to be involved in cancer progression and incident CV events, little is known about their relationship with cardio-oncology, especially on cancer treatment-related cardiovascular toxicity (CTRCT). This review aims to explore the evidence of the impact of NETs on cancer, CV events, and CTRCT, and the possible solutions based on the mechanism of NETs activation and NETs released toxic substances. Full article
(This article belongs to the Special Issue Emerging Role of Immunotherapies in Cancer and Their Cardiotoxic Effects)
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