DISSECTING IMMUNE DYSREGULATION IN PATIENTS WITHTHYMIC EPITHELIAL TUMORS BY AUTOANTIBODY ANDSINGLE-CELL PROFILING
type: CreativeWork
description: Thymic epithelial lesions (TELs) are a heterogeneous and rare group of diseases arising from the epithelial cells of the thymus. TELs include both benign conditions, such as thymic hyperplasia (TH), and malignant lesions, collectively referred to as thymic epithelial tumors (TETs). According to the 2021 WHO classification, TETs are further subdivided into thymomas comprising type A, AB, B1, B2, and B3 and thymic carcinomas (TC), based on tumor architecture, the morphology of malignant cells and the proportion of intratumoral immune cells. Prognosis progressively worsened from type A thymomas to TCs. Patients with thymomas showed an elevated susceptibility to paraneoplastic syndromes, in particular autoimmune diseases (ADs), which affects around 30% of thymoma patients. Evidence indicates that thymomas, but not TCs, can sustain intratumoral T-cell development, a process that appears dysregulated and likely contributes to thymoma-associated immune dysfunction, although the precise mechanisms linking TETs to ADs remain unclear. To address these knowledge gaps, we combined complementary approaches, including clinical and high-throughput autoAbs screening, a 39-color spectral flow cytometry panel to deeply characterize αβ, γδ and MAIT compartments, and single-cell RNA sequencing paired with αβ TCR sequencing to reconstruct developmental trajectories, functional states and clonal relationships. Pediatric thymuses were used as the healthy tissue counterpart whereas PBMCs from age-matched healthy donors were used as healthy peripheral blood controls. Public single-cell datasets were integrated to enable direct transcriptomic comparisons between patients and healthy individuals. Our results indicate that TEL patients can be classified into two main categories. One group, comprising TH and type AB, B1, B2 thymomas, retained intratumoral thymopoiesis, whereas type A, A-MNT, B3 thymomas and TC were predominantly infiltrated by mature T cells. Within this spectrum each histotype…
abstract: Thymic epithelial lesions (TELs) are a heterogeneous and rare group of diseases arising from the epithelial cells of the thymus. TELs include both benign conditions, such as thymic hyperplasia (TH), and malignant lesions, collectively referred to as thymic epithelial tumors (TETs). According to the 2021 WHO classification, TETs are further subdivided into thymomas comprising type A, AB, B1, B2, and B3 and thymic carcinomas (TC), based on tumor architecture, the morphology of malignant cells and the proportion of intratumoral immune cells. Prognosis progressively worsened from type A thymomas to TCs. Patients with thymomas showed an elevated susceptibility to paraneoplastic syndromes, in particular autoimmune diseases (ADs), which affects around 30% of thymoma patients. Evidence indicates that thymomas, but not TCs, can sustain intratumoral T-cell development, a process that appears dysregulated and likely contributes to thymoma-associated immune dysfunction, although the precise mechanisms linking TETs to ADs remain unclear. To address these knowledge gaps, we combined complementary approaches, including clinical and high-throughput autoAbs screening, a 39-color spectral flow cytometry panel to deeply characterize αβ, γδ and MAIT compartments, and single-cell RNA sequencing paired with αβ TCR sequencing to reconstruct developmental trajectories, functional states and clonal relationships. Pediatric thymuses were used as the healthy tissue counterpart whereas PBMCs from age-matched healthy donors were used as healthy peripheral blood controls. Public single-cell datasets were integrated to enable direct transcriptomic comparisons between patients and healthy individuals. Our results indicate that TEL patients can be classified into two main categories. One group, comprising TH and type AB, B1, B2 thymomas, retained intratumoral thymopoiesis, whereas type A, A-MNT, B3 thymomas and TC were predominantly infiltrated by mature T cells. Within this spectrum each histotype…
author: BALIN, SIMONE
language: eng
keywords: Thymic epithelial tumor, Autoimmunity, T cell, Immunology, Single-cell technologie, Spectral Flow Cytometry., Settore MEDS-02/A - Patologia generale
date published: 2026-01-27
date modified: 2026-07-27T20:19:00Z
provider: Università degli Studi di Milano
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: Università degli Studi di Milano

PropertyValue
property ID: Handle
value: https://hdl.handle.net/2434/1204982