{
  "abstract": "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.",
  "authors": [
    {
      "affiliations": [
        "Sotio Biotech a.s, Prague, Czech Republic"
      ],
      "name": "Linn A Syding"
    },
    {
      "affiliations": [
        "Sotio Biotech a.s, Prague, Czech Republic",
        "Department of Otorhinolaryngology and Head and Neck Surgery, Motol University Hospital, Prague, Czech Republic",
        "1st Faculty of Medicine, Charles University, Prague, Czech Republic"
      ],
      "name": "Klára Plačková"
    },
    {
      "affiliations": [
        "Sotio Biotech a.s, Prague, Czech Republic",
        "Department of Otorhinolaryngology and Head and Neck Surgery, Motol University Hospital, Prague, Czech Republic",
        "1st Faculty of Medicine, Charles University, Prague, Czech Republic"
      ],
      "name": "Lucie Pavelková"
    },
    {
      "affiliations": [
        "Sotio Biotech a.s, Prague, Czech Republic"
      ],
      "name": "Cecilia Aquino-Perez"
    },
    {
      "affiliations": [
        "Department of Medical Oncology, Leiden University Medical Center, Leiden, The Netherlands"
      ],
      "name": "Saskia J Santegoets"
    },
    {
      "affiliations": [
        "Fingerland Department of Pathology, University Hospital Hradec Kralove, Hradec Kralove, Czech Republic"
      ],
      "name": "Jan Laco"
    },
    {
      "affiliations": [
        "Department of Pathology and Molecular Medicine, Motol University Hospital, Prague, Czech Republic"
      ],
      "name": "Marek Grega"
    },
    {
      "affiliations": [
        "Department of Pathology, General University Hospital, Prague, Czech Republic"
      ],
      "name": "Pavel Dundr"
    },
    {
      "affiliations": [
        "Department of Pathology, General University Hospital, Prague, Czech Republic"
      ],
      "name": "Kristýna Němejcová"
    },
    {
      "affiliations": [
        "Department of Oncology and Radiotherapy, University Hospital Hradec Kralove, Hradec Kralove, Czech Republic"
      ],
      "name": "Miroslav Hodek"
    },
    {
      "affiliations": [
        "Department of Otorhinolaryngology and Head and Neck Surgery, Motol University Hospital, Prague, Czech Republic"
      ],
      "name": "Jan Bouček"
    },
    {
      "affiliations": [
        "Department of Otorhinolaryngology and Head and Neck Surgery, Motol University Hospital, Prague, Czech Republic"
      ],
      "name": "Michal Zábrodský"
    },
    {
      "affiliations": [
        "Fingerland Department of Pathology, University Hospital Hradec Kralove, Hradec Kralove, Czech Republic"
      ],
      "name": "Hana Vošmiková"
    },
    {
      "affiliations": [
        "Department of Obstetrics and Gynecology, University Hospital Kralovske Vinohrady, Prague, Czech Republic"
      ],
      "name": "Michael J Halaška"
    },
    {
      "affiliations": [
        "Department of Obstetrics and Gynecology, University Hospital Kralovske Vinohrady, Prague, Czech Republic"
      ],
      "name": "Lukáš Rob"
    },
    {
      "affiliations": [
        "Department of Otorhinolaryngology and Head and Neck Surgery, University Hospital Hradec Kralove, Hradec Kralove, Czech Republic"
      ],
      "name": "Petr Čelakovský"
    },
    {
      "affiliations": [
        "Department of Otorhinolaryngology and Head and Neck Surgery, University Hospital Hradec Kralove, Hradec Kralove, Czech Republic"
      ],
      "name": "Viktor Chrobok"
    },
    {
      "affiliations": [
        "Department of Gynecology and Obstetrics, University Hospital Hradec Kralove, Hradec Kralove, Czech Republic"
      ],
      "name": "Munachiso Ndukwe Iheme"
    },
    {
      "affiliations": [
        "Department of Gynecology and Obstetrics, University Hospital Hradec Kralove, Hradec Kralove, Czech Republic"
      ],
      "name": "Ivan Práznovec"
    },
    {
      "affiliations": [
        "Department of Oncology and Radiotherapy, University Hospital Hradec Kralove, Hradec Kralove, Czech Republic"
      ],
      "name": "Milan Vošmik"
    },
    {
      "affiliations": [
        "Sotio Biotech a.s, Prague, Czech Republic",
        "Masaryk University, Brno, Czech Republic"
      ],
      "name": "Stanislav Katina"
    },
    {
      "affiliations": [
        "Department of Gynaecology, Obstetrics and Neonatology, General University Hospital, Prague, Czech Republic"
      ],
      "name": "David Cibula"
    },
    {
      "affiliations": [
        "Fingerland Department of Pathology, University Hospital Hradec Kralove, Hradec Kralove, Czech Republic"
      ],
      "name": "Aleš Ryška"
    },
    {
      "affiliations": [
        "Department of Medical Oncology, Leiden University Medical Center, Leiden, The Netherlands"
      ],
      "name": "Sjoerd H van der Burg"
    },
    {
      "affiliations": [
        "Sotio Biotech a.s, Prague, Czech Republic"
      ],
      "name": "Radek Špíšek"
    },
    {
      "affiliations": [
        "Sotio Biotech a.s, Prague, Czech Republic"
      ],
      "name": "Anna Fialová"
    }
  ],
  "title": "High Treg and PMN-MDSC densities are a hallmark of tertiary lymphoid structures in fatal cases of cervical cancer",
  "uid": "70bd3462-4780-5edc-822c-2ca6958a9b89"
}