High Treg and PMN-MDSC densities are a hallmark of tertiary
lymphoid structures in fatal cases of cervical cancer

J 2025

High Treg and PMN-MDSC densities are a hallmark of tertiary lymphoid structures in fatal cases of cervical cancer

SYDING, Linn A; Klára PLAČKOVÁ; Lucie PAVELKOVÁ; Cecilia AQUINO-PEREZ; Saskia J SANTEGOETS et al.

Základní údaje

Originální název

High Treg and PMN-MDSC densities are a hallmark of tertiary lymphoid structures in fatal cases of cervical cancer

Autoři

Vydání

Journal for ImmunoTherapy of Cancer, BMJ Publishing Group, 2025, 2051-1426

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30100 3.1 Basic medicine

Stát vydavatele

Velká Británie a Severní Irsko

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 10.600 v roce 2024

Označené pro přenos do RIV

Ano

Organizační jednotka

Přírodovědecká fakulta

Klíčová slova anglicky

High densities of tertiary lymphoid structures; head and neck squamous cell carcinoma; cervical cancer; survival analysis; Kaplan-Meier survival curves; statistical inference

Štítky

14311010, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 11. 11. 2025 09:07, Mgr. Marie Novosadová Šípková, DiS.

Anotace

V originále

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.

Přiložené soubory

2522177.pdf

Citovat

SYDING, Linn A; Klára PLAČKOVÁ; Lucie PAVELKOVÁ; Cecilia AQUINO-PEREZ; Saskia J SANTEGOETS; Jan LACO; Marek GREGA; Pavel DUNDR; Kristýna NĚMEJCOVÁ; Miroslav HODEK; Jan BOUČEK; Michal ZÁBRODSKÝ; Hana VOŠMIKOVÁ; Michael J HALAŠKA; Lukáš ROB; Petr ČELAKOVSKÝ; Viktor CHROBOK; Munachiso Ndukwe IHEME; Ivan PRÁZNOVEC; Milan VOŠMIK; Stanislav KATINA; David CIBULA; Aleš RYŠKA; Sjoerd H VAN DER BURG; Radek ŠPÍŠEK a Anna FIALOVÁ. High Treg and PMN-MDSC densities are a hallmark of tertiary lymphoid structures in fatal cases of cervical cancer. Journal for ImmunoTherapy of Cancer. BMJ Publishing Group, 2025, roč. 13, č. 9, s. 1-15. ISSN 2051-1426. Dostupné z: https://doi.org/10.1136/jitc-2025-012613.

@article{2522177,
   author = {Syding, Linn A and Plačková, Klára and Pavelková, Lucie and AquinoandPerez, Cecilia and Santegoets, Saskia J and Laco, Jan and Grega, Marek and Dundr, Pavel and Němejcová, Kristýna and Hodek, Miroslav and Bouček, Jan and Zábrodský, Michal and Vošmiková, Hana and Halaška, Michael J and Rob, Lukáš and Čelakovský, Petr and Chrobok, Viktor and Iheme, Munachiso Ndukwe and Práznovec, Ivan and Vošmik, Milan and Katina, Stanislav and Cibula, David and Ryška, Aleš and van der Burg, Sjoerd H and Špíšek, Radek and Fialová, Anna},
   article_number = {9},
   doi = {https://doi.org/10.1136/jitc-2025-012613},
   keywords = {High densities of tertiary lymphoid structures; head and neck squamous cell carcinoma; cervical cancer; survival analysis; Kaplan-Meier survival curves; statistical inference},
   language = {eng},
   issn = {2051-1426},
   journal = {Journal for ImmunoTherapy of Cancer},
   title = {High Treg and PMN-MDSC densities are a hallmark of tertiary lymphoid structures in fatal cases of cervical cancer},
   url = {https://jitc.bmj.com/content/13/9/e012613},
   volume = {13},
   year = {2025}
}

TY  - JOUR
ID  - 2522177
AU  - Syding, Linn A - Plačková, Klára - Pavelková, Lucie - Aquino-Perez, Cecilia - Santegoets, Saskia J - Laco, Jan - Grega, Marek - Dundr, Pavel - Němejcová, Kristýna - Hodek, Miroslav - Bouček, Jan - Zábrodský, Michal - Vošmiková, Hana - Halaška, Michael J - Rob, Lukáš - Čelakovský, Petr - Chrobok, Viktor - Iheme, Munachiso Ndukwe - Práznovec, Ivan - Vošmik, Milan - Katina, Stanislav - Cibula, David - Ryška, Aleš - van der Burg, Sjoerd H - Špíšek, Radek - Fialová, Anna
PY  - 2025
TI  - High Treg and PMN-MDSC densities are a hallmark of tertiary lymphoid structures in fatal cases of cervical cancer
JF  - Journal for ImmunoTherapy of Cancer
VL  - 13
IS  - 9
SP  - 1-15
EP  - 1-15
PB  - BMJ Publishing Group
SN  - 20511426
KW  - High densities of tertiary lymphoid structures
KW  - head and neck squamous cell carcinoma
KW  - cervical cancer
KW  - survival analysis
KW  - Kaplan-Meier survival curves
KW  - statistical inference
UR  - https://jitc.bmj.com/content/13/9/e012613
N2  - 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.
ER  -

SYDING, Linn A; Klára PLAČKOVÁ; Lucie PAVELKOVÁ; Cecilia AQUINO-PEREZ; Saskia J SANTEGOETS; Jan LACO; Marek GREGA; Pavel DUNDR; Kristýna NĚMEJCOVÁ; Miroslav HODEK; Jan BOUČEK; Michal ZÁBRODSKÝ; Hana VOŠMIKOVÁ; Michael J HALAŠKA; Lukáš ROB; Petr ČELAKOVSKÝ; Viktor CHROBOK; Munachiso Ndukwe IHEME; Ivan PRÁZNOVEC; Milan VOŠMIK; Stanislav KATINA; David CIBULA; Aleš RYŠKA; Sjoerd H VAN DER BURG; Radek ŠPÍŠEK a Anna FIALOVÁ. High Treg and PMN-MDSC densities are a hallmark of tertiary lymphoid structures in fatal cases of cervical cancer. \textit{Journal for ImmunoTherapy of Cancer}. BMJ Publishing Group, 2025, roč.~13, č.~9, s.~1-15. ISSN~2051-1426. Dostupné z: https://doi.org/10.1136/jitc-2025-012613.

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