PhD Scientific Days 2026

Poster Session 3.H - Pharmaceutical Sciences and Health Technologies

Thymic Central Tolerance Disruption Drives Anti-PD-1 Cardiotoxicity

Előadó neve

Mr. Kocsis, Marton, MSc

Neptune code

dx26uf

Előadó munkahelye

Department of Pharmacology and Pharmacotherapy

Előadó telefonszáma

+36308252435

Előadó e-mail címe

kocsis.marton@semmelweis.hu

Az előadás címe

Thymic Central Tolerance Disruption Drives Anti-PD-1 Cardiotoxicity

Szerző(k) neve és munkahelye

Marton S Kocsis¹, Anna Kulin¹, Lilla Szabo¹, Tamas G Gergely¹, Sayour V Nabil¹, Viktoria E Toth¹, David Nagy¹, Tamas Kovacs¹, Marta Szabo¹, Zsombor I Hegedus¹, Luca Varga¹, Dora Bihary¹, Bence Agg¹, Peter Ferdinandy¹, Zoltan V Varga¹

1: Department of Pharmacology and Pharmacotherapy

Bemutatás módja

Poszter

Szekció

Poster Session 3.H - Pharmaceutical Sciences and Health Technologies

Language of the presentation

English

Preferred session

Pharmaceutical Sciences and Health Technologies

Összefoglaló szövege

Introduction: Immune checkpoint inhibitors (ICIs) revolutionized cancer treatment, the success is however overshadowed by immune related adverse events, severe complications, attributed to peripheral overactivation of autoimmune T-cells. Recent clinical observations, however, link these complications to thymic discrepancies such as thymoma or thymic hyperplasia. We hypothesize that anti-PD-1 therapy actively disrupts thymic central tolerance and drives ICi-induced cardiotoxicity.
Aim: Our aim was to determine whether thymic activity plays a role in ICI-induced cardiotoxicity and whether thymic activity modulation, either by physiological aging or by pharmacological degradation, confers protection.
Methods: Young and aged mice were treated with anti-PD-1 therapy for two weeks. 5-Azacitidine was used for pharmacological involution of the thymus. Our main endpoints were echocardiography, RNAseq, RNAscope, qRT-PCR, histology, immunhistology, and flow cytometry.
Results: Two weeks of anti-PD-1 therapy induced a systolic decline in young animals but not in aged. We observed robust transcriptional reprogramming in young thymuses affecting key leukocyte functions and ribosomal biogenesis paired with distinct Cxcl9 medullary aggregates. Flow cytometry and immunohistochemistry revealed a shift in double-negative and an expansion in double-positive thymocytes with reduced Tregs. Heart tissue of young mice showed elevated levels of inflammatory chemokines (Cxcl9/10) and cytokines (IFN-y, Il23) without cellular infiltration. These observed changes were completely ameliorated by either physiological or pharmacological involution of the thymus.
Conclusions: Anti-PD-1 therapy induced cardiac dysfunction is linked to the disruption of thymic central tolerance, expanding the current paradigm of only peripheral reactivation. Physiological or pharmacological involution protects against this toxicity establishing the thymus as a target for risk stratification and careful targeted modulation.
Funding: The work was supported by EU’s Horizon (739593) and by the MTA (LP-2021-14) and by the NKL (2022-1.1.1-KK-2022-00005)

University

Semmelweis University

Supervisor

Dr. Zoltan V 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

in doctoral studies after complex exam (PhD)

Kind

Szabad

Status

elfogadva

Accepted presentation method

poszter

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

8118

Start

14:18

End

14:21