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Vaccines
Special Issues
Cancer Immunotherapy and Immune Related Cardiac Complications
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Cancer Immunotherapy and Immune Related Cardiac Complications

A special issue of Vaccines (ISSN 2076-393X). This special issue belongs to the section "Cancer Vaccines and Immunotherapy".

Deadline for manuscript submissions: closed (31 March 2022) | Viewed by 6299

Special Issue Editor

Dr. Rabea Asleh

E-Mail Website
Guest Editor
Department of Cardiology, Hadassah University Medical Center, Ein Kerem, P.O.B. 12000, Jerusalem 9112001, Israel
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Immunotherapy has revolutionized cancer treatment and have significantly improved the clinical outcomes of patients with advanced cancers. However, immune checkpoint inhibitors (ICIs) that target PD-1 (programmed cell death protein-1), PD-L1 (programmed cell death protein ligand-1) or/and CTLA-4 (cytotoxic T lymphocyte-associated antigen-4) are commonly associated with acute immune-mediated adverse events. ICIs have become standard of care for melanoma, non-small cell lung cancer, renal cell cancer, and many other malignancies. As the use of immunotherapy increases, an increasing incidence of immune-related toxicities will be encountered. Although more effective than single-agent immunotherapy, the risk of cardiotoxicity is substantially increased with dual immunotherapy. The use of these agents is associated with increased risk of myocarditis, arrhythmias (including heart block and ventricular tachycardia), pericarditis, and vasculitis; also occur along with much more common noncardiac toxicities and concurrent with other chronic inflammatory diseases. The impact of immunotherapy on existing inflammatory diseases is unknown. Moreover, during the current era of COVID-19, which has proven systemic proinflammatory consequences on the heart and other organs, the concomitant use of ICIs for cancer treatment may have more substantial adverse effects on the cardiovascular system. Studies are currently focusing on understanding the mechanisms underlying the development of cardiotoxicity and risk factors, including potential genetic predisposition for immune-related toxicity as a result of ICIs therapy. Finally, given potential fatal cardiac complications with ICIs, studies focusing on identification of prognostic markers that can help in risk stratification are encouraged. Early identification of patients susceptible to immunotherapy-related cardiotoxicity is clinically meaningful, as more careful monitoring and early management can help improve cardiac outcomes.

Dr. Rabea Asleh
Guest Editor

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. Vaccines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). 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

  • Immunotherapy
  • Immune checkpoint inhibitors
  • Cancer
  • Cardiotoxicity
  • Myocarditis
  • Prognostic biomarkers
  • Predictors
  • Inflammatory diseases
  • COVID-19

Published Papers (2 papers)

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Review

23 pages, 16023 KiB  
Review
Exploring the Mechanisms Underlying the Cardiotoxic Effects of Immune Checkpoint Inhibitor Therapies
by Daniel Ronen, Aseel Bsoul, Michal Lotem, Suzan Abedat, Merav Yarkoni, Offer Amir and Rabea Asleh
Vaccines 2022, 10(4), 540; https://doi.org/10.3390/vaccines10040540 - 31 Mar 2022
Cited by 8 | Viewed by 3370
Abstract
Adaptive immune response modulation has taken a central position in cancer therapy in recent decades. Treatment with immune checkpoint inhibitors (ICIs) is now indicated in many cancer types with exceptional results. The two major inhibitory pathways involved are cytotoxic T-lymphocyte-associated protein 4 (CTLA4) [...] Read more.
Adaptive immune response modulation has taken a central position in cancer therapy in recent decades. Treatment with immune checkpoint inhibitors (ICIs) is now indicated in many cancer types with exceptional results. The two major inhibitory pathways involved are cytotoxic T-lymphocyte-associated protein 4 (CTLA4) and programmed cell death protein 1 (PD-1). Unfortunately, immune activation is not tumor-specific, and as a result, most patients will experience some form of adverse reaction. Most immune-related adverse events (IRAEs) involve the skin and gastrointestinal (GI) tract; however, any organ can be involved. Cardiotoxicity ranges from arrhythmias to life-threatening myocarditis with very high mortality rates. To date, most treatments of ICI cardiotoxicity include immune suppression, which is also not cardiac-specific and may result in hampering of tumor clearance. Understanding the mechanisms behind immune activation in the heart is crucial for the development of specific treatments. Histological data and other models have shown mainly CD4 and CD8 infiltration during ICI-induced cardiotoxicity. Inhibition of CTLA4 seems to result in the proliferation of more diverse T0cell populations, some of which with autoantigen recognition. Inhibition of PD-1 interaction with PD ligand 1/2 (PD-L1/PD-L2) results in release from inhibition of exhausted self-recognizing T cells. However, CTLA4, PD-1, and their ligands are expressed on a wide range of cells, indicating a much more intricate mechanism. This is further complicated by the identification of multiple co-stimulatory and co-inhibitory signals, as well as the association of myocarditis with antibody-driven myasthenia gravis and myositis IRAEs. In this review, we focus on the recent advances in unraveling the complexity of the mechanisms driving ICI cardiotoxicity and discuss novel therapeutic strategies for directly targeting specific underlying mechanisms to reduce IRAEs and improve outcomes. Full article
(This article belongs to the Special Issue Cancer Immunotherapy and Immune Related Cardiac Complications)
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14 pages, 1473 KiB  
Review
The Diagnosis and Management of Immune Checkpoint Inhibitor Cardiovascular Toxicity: Myocarditis and Beyond
by Dan Gilon, Zaza Iakobishvili and David Leibowitz
Vaccines 2022, 10(2), 304; https://doi.org/10.3390/vaccines10020304 - 16 Feb 2022
Cited by 4 | Viewed by 2278
Abstract
Recent years have brought major advancements in the use of immune therapy and specifically immune checkpoint inhibitors (ICIs) in cancer patients, with expanding indications for various malignancies resulting in the treatment of a large and increasing number of patients. While this therapy significantly [...] Read more.
Recent years have brought major advancements in the use of immune therapy and specifically immune checkpoint inhibitors (ICIs) in cancer patients, with expanding indications for various malignancies resulting in the treatment of a large and increasing number of patients. While this therapy significantly improves outcomes in a variety of hematologic and solid tumors, the use of ICIs is associated with a substantial risk of immune-related adverse events. Cardiovascular toxicity, while not the most common side effect of ICIs, is associated with significant morbidity and mortality. It is therefore crucial for oncologists and cardiologists, as well as internists and emergency room physicians, to have a good understanding of this increasingly common clinical problem. In the present review, we discuss the cardiac aspects of ICI therapy with special emphasis on the clinical manifestations of their cardiovascular toxicity, diagnostic approaches, treatment and suggested surveillance. Full article
(This article belongs to the Special Issue Cancer Immunotherapy and Immune Related Cardiac Complications)
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