High Treg and PMN-MDSC densities are a hallmark of tertiary lymphoid structures in fatal cases of cervical cancer
Language English Country Great Britain, England Media electronic
Document type Journal Article
PubMed
40998518
PubMed Central
PMC12481325
DOI
10.1136/jitc-2025-012613
PII: jitc-2025-012613
Knihovny.cz E-resources
- Keywords
- Cervical Cancer, Head and Neck Cancer, Myeloid-derived suppressor cell - MDSC, T regulatory cell - Treg,
- MeSH
- Squamous Cell Carcinoma of Head and Neck immunology MeSH
- Tertiary Lymphoid Structures * immunology pathology MeSH
- Papillomavirus Infections * complications immunology MeSH
- Middle Aged MeSH
- Humans MeSH
- Myeloid-Derived Suppressor Cells * immunology metabolism MeSH
- Uterine Cervical Neoplasms * immunology pathology mortality MeSH
- Prognosis MeSH
- T-Lymphocytes, Regulatory * immunology metabolism MeSH
- Aged MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
BACKGROUND: High densities of tertiary lymphoid structures (TLSs) are associated with improved clinical outcomes in various malignancies, including human papillomavirus (HPV)-associated head and neck squamous cell carcinoma (HNSCC). However, the role of TLSs in shaping antitumor immunity in HPV-induced cervical cancer (CESC) remains unclear. Therefore, we analyzed the density, composition, and prognostic impact of TLSs in patients with CESC as well as patients with HNSCC. METHODS: Multiplex immunofluorescence, immunohistochemistry, and spatial transcriptomics were used to analyze TLS density and composition in HNSCC and CESC tissue sections with respect to patient prognosis. The spatial approach was supplemented by flow cytometry-based analysis of the polymorphonuclear myeloid-derived suppressor cell (PMN-MDSC) phenotype in freshly resected primary tumor tissues. RESULTS: Although both indications were associated with HPV infection, we confirmed a positive correlation between TLS density and improved overall survival only in patients with HNSCC. The TLS composition differed markedly between HNSCC and CESC samples, with a shift toward high regulatory T cell (Treg) and PMN-MDSC abundance in CESC samples. The highest Treg and PMN-MDSC levels were observed in patients with CESC who died of the disease. CESC-infiltrating PMN-MDSCs showed high arginase 1 expression, which correlated with diminished T-cell receptor (TCR)ζ chain expression in CESC-infiltrating T cells. Additionally, the high number of PMN-MDSCs in TLSs was associated with the absence of HPV-specific T cells in CESC. CONCLUSIONS: Unlike in HNSCC, the composition of TLSs, rather than their quantity, was associated with the overall survival of patients with CESC. High numbers of Tregs and PMN-MDSCs infiltrating immature TLSs prevail in patients with CESC who succumbed to the disease and seem to affect tumor-specific immune responses.
1st Faculty of Medicine Charles University Prague Czech Republic
Department of Medical Oncology Leiden University Medical Center Leiden The Netherlands
Department of Pathology and Molecular Medicine Motol University Hospital Prague Czech Republic
Department of Pathology General University Hospital Prague Czech Republic
Fingerland Department of Pathology University Hospital Hradec Kralove Hradec Kralove Czech Republic
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