News | Coronavirus (COVID-19) | November 03, 2022

Study Sheds Light on the Reasons Behind Sex Differences in Myocarditis

Study suggests mechanisms behind why myocarditis associated with cancer immunotherapies may occur more frequently in female patients

A mouse heart with immune infiltrates leading to ICI-myocarditis. Image courtesy of UCSF

A mouse heart with immune infiltrates leading to ICI-myocarditis. Image courtesy of UCSF


November 3, 2022 — In the past several years, myocarditis has been of public interest because of cases associated with vaccines for SARS-CoV2 or related conditions. Another form of myocarditis has been linked to immune checkpoint inhibitors (ICIs) used in cancer care. ICI-induced myocarditis is a potentially fatal side effect of ICI usage, and it appears that the adverse cardiac effects may disproportionally impact female patients. This finding is in contrast to other forms of myocarditis, with more cases reported in male patients.   

In a study co-led by researchers from UC San Francisco and The University of Texas MD Anderson Cancer Center, and appearing November 2 in Science Translational Medicine, the researchers shed new light on the underling biology behind these sex differences.

The cardio-oncology group at UCSF has been investigating ICI-induced myocarditis and generated several mouse models of the new syndrome hoping to use these models for better strategies to help patients. One of these models was a genetic mouse model.

“This model copied much of the characteristics of the syndrome in humans and led to sudden death,” said Javid Moslehi, MD, William Grossman Distinguished Professor and section chief of Cardio-Oncology and Immunology for the UCSF Heart and Vascular Center. “What was strange, however, was that in this model, the female mice were affected.”

At the same time, the MD Anderson team, led by Liuqing Yang, PhD, and Chunru Lin, MD, PhD, both associate professors of Molecular and Cellular Oncology, had generated other models of ICI-myocarditis. The researchers bred tumor-bearing mice treated with ICI (combinatorial anti-PD-1 and anti-CTLA-4 antibody treatment) which exhibited several cardiovascular toxicities, including myocarditis and arrhythmia. In this model, female mice were also affected more compared to male mice. 

“The sex differences observed in both ICI-myocarditis mouse models are especially intriguing because in non-ICI myocarditis (viral or autoimmune) in the general population, male sex is considered a risk factor and defines a more fulminant course,” said Moslehi, “If such an opposite sex-difference in ICI-myocarditis is true, it suggests a possible interaction of immune checkpoints and sex hormones.”

It turned out Moslehi was spot on. Initial studies by MD Anderson team identified two cardiac factors (termed MANF and HSPA5) that normally help protect the heart from immune invasion. These factors were diminished in the ICI-myocarditis models as well as human heart tissue from affected patients with ICI-myocarditis. The factors were further diminished in female mice and regulated by female sex hormones. Adding the factors back to mice attenuated disease, suggesting a causal role.

“These models and our data suggest a previously unappreciated role for endocrine-cardiac-immune pathways and perhaps suggest ways that one could curtail cardiac inflammation,” said Yang and Lin.

While the sex differences in mice models are convincing, Moslehi stressed that more research is needed to extend this work to humans. “We need more human studies to convincingly show that ICI-myocarditis preferentially affects females,” said Moslehi. “Teasing this out in humans is particularly hard since many patients traditionally receiving the treatments have been male, both because in general more men are enrolled into clinical trials and the types of cancers which were initially treated with ICI occurred more frequently in males.”

For more information: www.ucsf.edu

Related COVID/Myocarditis Content:    

Getting to the Heart of COVID-19 Vaccination and its Cardiovascular Risks

COVID-19 Surges Linked to Spike in Heart Attacks

COVID-19 Fallout May Lead to More Cancer Deaths    

Kawasaki-like Inflammatory Disease Affects Children With COVID-19    

FDA Adds Myocarditis Warning to COVID mRNA Vaccine Clinician Fact Sheets    

CMS Now Requires COVID-19 Vaccinations for Healthcare Workers by January 4    

Cardiac MRI of Myocarditis After COVID-19 Vaccination in Adolescents    

Small Number of Patients Have Myocarditis-like Illness After COVID-19 Vaccination    

Overview of Myocarditis Cases Caused by the COVID-19 Vaccine    

Case Study Describes One of the First U.S. Cases of MIS-C    

NIH-funded Project Wants to Identify Children at Risk for MIS-C From COVID-19    


Related Content

News | Cardio-oncology

June 19, 2024 — Modern therapies have extended the lives of many cancer patients; however, survivors often live with ...

Home June 19, 2024
Home
News | Cardio-oncology

February 1, 2023 — The International Cardio-Oncology Society has awarded University Hospitals (UH) Harrington Heart & ...

Home February 01, 2023
Home
News | Cardio-oncology

May 23, 2022 — New data from a study of more than 100 million hospitalizations using machine learning augmentation was ...

Home May 23, 2022
Home
News | Cardio-oncology

February 25, 2020 — Results of a multi-centre, international, clinical trial co-led by Peter Munk Cardiac Centre (PMCC) ...

Home February 25, 2021
Home
News | Cardio-oncology

July 29, 2019 — Cancer patients taking cholesterol-lowering statin medication following radiation therapy of the chest ...

Home July 29, 2019
Home
Videos | Cardio-oncology

Magid Awadalla, MBBS, is an advanced cardiac imaging research fellow at Massachusetts General Hospital. He has been ...

Home March 22, 2019
Home
News | Cardio-oncology

March 13, 2019 — An imaging procedure commonly performed before starting cancer treatment can provide valuable clues ...

Home March 13, 2019
Home
News | Cardio-oncology

January 28, 2019 — The American College of Cardiology host the third Advancing the Cardiovascular Care of the Oncology ...

Home January 28, 2019
Home
News | Cardio-oncology

January 3, 2019 — Breast cancer patients who take a heart drug at the same time as trastuzumab have less heart damage ...

Home January 03, 2019
Home
News | Cardio-oncology

December 21, 2018 — Older adults with cancer are more likely to have had a heart attack or stroke in the months prior to ...

Home December 21, 2018
Home
Subscribe Now