PhD Scientific Days 2025

Poster Session II. - J: Theoretical and Translational Medicine

Myocardial immune checkpoint expression in advanced heart failure patients

Előadó neve

Dr. Gergely Tamás

Neptun code

CQN2WF

Előadó munkahelye

Semmelweis University, Department of Pharmacology and Pharmacotherapy

Előadó telefonszáma

+36209504707

Előadó e-mail címe

tamas.gergely95@gmail.com

Az előadás címe

Myocardial immune checkpoint expression in advanced heart failure patients

Szerző(k) neve és munkahelye

Tamás Gergely¹, Tamás Kovács¹, Zsombor Hegedűs¹, Viktória Tóth¹, Zsófia Onódi¹, Bálint Barta², Ali Alex Sayour², Tamás Radovits², Przemysław Leszek³, Béla Merkely², Péter Ferdinandy¹, Zoltán Varga¹

1: Semmelweis University, Department of Pharmacology and Pharmacotherapy
2: Semmelweis University, Heart and Vascular Center
3: Department of Heart Failure and Transplantology, National Institute of Cardiology, Warsaw

Bemutatás módja

Poszter

Szekció

Poster Session II. - J: Theoretical and Translational Medicine

Language of the presentation

English

Preferred session

Theoretical and Translational Medicine

Összefoglaló szövege

Introduction: Immune checkpoints (ICs) are key regulatory molecules of the adaptive immune response. Immune checkpoint inhibition (ICI) is a revolutionary anti-cancer treatment strategy. However, ICIs can lead to various immune-related adverse events, including cardiovascular toxicities, such as myocarditis and heart failure (HF). Based on these, ICs may be essential for preserving cardiac homeostasis. Nevertheless, little is known about the expression of ICs in the healthy and failing human.
Aims: Here, we aimed to characterize the expression of co-inhibitory ICs in patients with advanced HF.
Methods: Myocardial tissue samples were obtained during heart transplantation from HF patients with ischemic or non-ischemic etiology (n = 7 / group for the screening cohort, n = 26 and 54, respectively, for the validation cohort). Healthy controls (n=6) were organ donors whose hearts were not transplanted due to technical issues. The expression level of different co-inhibitory IC proteins (PD-L1, CTLA-4, LAG3, VISTA, and B7-H3) in the heart was characterized via Western blot analysis.
Results: PD-L1 showed a significant increase in both HF groups while VISTA decreased compared with healthy controls. In the ischemic HF group, LAG3 was also significantly decreased, while it was unaltered in non-ischemic HF. CTLA-4, and B7-H3 did not show any significant changes in the HF samples. In the validation cohort, myocardial PD-L1 expression showed a significant negative correlation with left ventricular ejection fraction, right ventricular diameter, and pulmonary vascular resistance regardless of etiology. LAG3 was associated with cardiac wall thickness in both groups, whereas LAG3 and VISTA expression correlated with functional capacity in patients with non-ischemic HF.
Conclusion: Myocardial expression of immune checkpoints was altered during HF, associated with cardiac functional and structural alterations, and functional capacity. Investigating the role of immune checkpoints in cardiac disease could help to explain the cardiovascular toxicities of immune checkpoint inhibitors and may lead to novel mechanistic insights into the mechanisms of HF development.
Funding: 2024-2.1.1-EKÖP-2024-00004 University Research Scholarship Programme of the Ministry for Culture and Innovation from the source of the National Research, Development and Innovation Fund.

University

Semmelweis University

Supervisor

Dr. Zoltán Varga

Publication of my abstract

I do not give consent to the publication of my abstract on the website of the congress.

phd.section.field

after finishing doctoral studies with absolutorium (PhD)

Kind

Szabad

Status

elfogadva

Accepted presentation method

poszter

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

6119

Start

18:18

End

18:24