Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Koll, FJ; Weers, L; Weigert, A; Banek, S; Köllermann, J; Kluth, L; Wenzel, M; Garcia, CC; Szarvas, T; Wessolly, M; Ingenwerth, M; Jeroch, J; Döring, C; Chun, FK; Wild, PJ; Reis, H.
Histopathologic, Molecular, and Clinical Profiling of Lymphoepithelioma-like Carcinoma of the Bladder.
Mod Pathol. 2024; 37(11): 100588
Doi: 10.1016/j.modpat.2024.100588
Web of Science
PubMed
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- Führende Autor*innen der Med Uni Graz
- Koll Florestan Johannes
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- Abstract:
- Lymphoepithelioma-like carcinoma of the bladder (LELC-B) is a rare histologic subtype characterized by strong immune cell (IC) infiltrates. A better prognosis and favorable response rates to immune checkpoint inhibitors have been described. We aimed to characterize the molecular profiles and IC infiltration of LELC-B for a better understanding of its therapeutic implications. We identified 11 muscle-invasive bladder cancer cases with pure and mixed LELC-B. Programmed cell death ligand-1 (PD-L1) expression and mismatch repair proteins were evaluated using immunohistochemistry. We calculated the tumor mutational burden and characterized mutational profiles using whole-exome DNA sequencing data. Transcriptomic signatures were detected using the NanoString nCounter PanCancer IO360 Panel. Multiplex immunofluorescence of tumor microenvironment (PD-L1, PanCK, α-SMA, vimentin, CD45, and Ki67) and T cells (CD4, CD3, PD-1, CD163, CD8, and FoxP3) was used to quantify cell populations. All LELC-B cases were highly positive for PD-L1 (median tumor proportion score/tumor cell, 70%; range, 20%-100%; median combined positive score, 100; range, 50-100) and mismatch repair proficient and negative for Epstein-Barr virus infection. IC infiltrates were characterized by a high CD8+ T-cell count and high PD-1/PD-L1 expression on immune and tumor cells. LELC-B showed upregulation of signaling pathways involved in IC response. Most common mutations were found in chromatin remodeling genes causing epigenetic dysregulation. All LELC-B cases showed high tumor mutational burden with a median of 39 mutations/Mb (IQR, 29-66 mutations/Mb). In conclusion, LELC-B is a highly immunogenic tumor, showing strong upregulation of PD-1/PD-L1 and making immune checkpoint inhibitors a promising treatment option.
- Find related publications in this database (using NLM MeSH Indexing)
- Humans - administration & dosage
- Urinary Bladder Neoplasms - genetics, pathology, immunology
- Male - administration & dosage
- Aged - administration & dosage
- Female - administration & dosage
- Middle Aged - administration & dosage
- Biomarkers, Tumor - genetics, analysis
- B7-H1 Antigen - genetics, metabolism
- Aged, 80 and over - administration & dosage
- Tumor Microenvironment - immunology
- Mutation - administration & dosage
- Lymphocytes, Tumor-Infiltrating - immunology, pathology
- Find related publications in this database (Keywords)
- bladder cancer
- the bladder
- tumor mutational burden
- subtypes
- muscle-invasive bladder cancer
- lymphoepithelioma-like carcinoma of