PhD Scientific Days 2024

Poster Session T - Cardiovascular Medicine and Research 3.

Melanoma Subtype-dependent Cardiotoxicity to Immune Checkpoint Inhibitor Therapy

Előadó neve

Mr. Kovács, Tamás

Neptun code

E3K62M

Előadó munkahelye

Department of Pharmacology and Pharmacotherapy, Semmelweis University

Előadó telefonszáma

+36702285757

Előadó e-mail címe

kovacs.tamas1@semmelweis.hu

Az előadás címe

Melanoma Subtype-dependent Cardiotoxicity to Immune Checkpoint Inhibitor Therapy

Szerző(k) neve és munkahelye

Kovács Tamás^1,2,3, Paál Ágnes^1,2,3, Hegedűs Zsombor^1,2,3, Szabó Lilla^1,2,3, Varga V. Zoltán^1,2,3

1: Department of Pharmacology and Pharmacotherapy, Semmelweis University, Budapest, Hungary
2: SE Momentum Cardio-Oncology and Cardioimmunology Research Group, Budapest, Hungary
3: HCEMM-SU Cardiometabolic Immunology Research Group, Budapest, Hungary

Bemutatás módja

Poszter

Szekció

Poster Session T - Cardiovascular Medicine and Research 3.

Language of the presentation

English

Preferred session

Cardiovascular Medicine and Research

Összefoglaló szövege

Introduction: Immune checkpoint inhibitors (ICIs) have been revolutionized cancer pharmacotherapy with unprecedented efficacy in the treatment of several malignancies. Despite the excellent therapeutic effects of ICIs, these drugs typically induce a broad spectrum of toxic reactions, mainly due to immune-related adverse events (irAEs). Out of the irAEs, the cardiovascular toxicities are the most severe form, they can be life-threatening complications. The pathomechanism of ICI-induced cardiotoxicity is mostly unknown so far. Therefore, identification of patients who are at risk to develop certain types of cardiotoxicities is currently not possible.
Aims: Our aim is to test the hypothesis, suggesting that T cells are targeting an antigen shared by the tumor and the heart in a preclinical model with two different melanoma cell lines.
Method: Immunologically “cold” B16F10 and human relevant mutations (BrafV600E/wt, Cdkn2a-/- Pten-/-) containing YUMM1.7 syngeneic melanoma cells were injected to the right flank of 8 weeks old C57Bl6 male mice. After initial tumor growth, we treated the the animals with anti-PD1 or corresponding isotype control. Cardiac specific gene expression was measured from in vivo grown tumor tissues.
Results: There is no significant difference in tumor growth between treatment groups. Based on echocardiography results, ICI treatment led to ejection fraction reduction in YUMM1.7 and no change in B16F10 group. Conversely, left ventricle mass increase was found in B16F10 and not in YUMM1.7 tumor group. We confirmed the hypertrophy with WGA and ILB4 lectin histochemistry and qPCR.
Conclusion: Our results show that anti-PD1 treatment of mice bearing different melanoma subtypes result in various phenotypes of ICI-induced cardiotoxicity. This phenotypic difference could be the consequence of different cardiac specific gene expression. More thorough testing of ICI therapy in different tumor types with gene expression analysis is needed in preclinical and clinical studies in order to develop stratification score to predict cardiac irAEs development after ICI therapy based on shared antigen hypothesis.
Funding: KT was supported by the New National Excellence Program of the Ministry for Innovation and Technology from the source of the National Research, Development and Innovation Fund (ÚNKP-23-4-I-SE-5).

University

Semmelweis University

Supervisor

Varga V. Zoltán

Publication of my abstract

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

Kind

Szabad

Status

elfogadva

Accepted presentation method

poszter

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

4612

Start

16:25

End

16:28