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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1455426
This article is part of the Research Topic Tumor-draining lymph nodes View all 4 articles

Prognostic Value of T Regulatory Cells and Immune Checkpoints Expression in Tumor-Draining Lymph Nodes for Oral Squamous Cell Carcinoma

Provisionally accepted
Krzysztof Piersiala Krzysztof Piersiala *Eric Hjalmarsson Eric Hjalmarsson Vilma Lagebro Vilma Lagebro Pedro Farrajota Pedro Farrajota Rusana Bark Rusana Bark Alexandra Elliot Alexandra Elliot Linda Marklund Linda Marklund Gregori Margolin Gregori Margolin Susanna Georen Susanna Georen Lars Olaf Cardell Lars Olaf Cardell
  • Karolinska Institutet (KI), Solna, Sweden

The final, formatted version of the article will be published soon.

    Despite the employment of extensive therapeutic strategies, OSCC recurrence and mortality rates persist at high levels. This underscores the shortcomings of current prognostic models and the urgency for refined biomarkers. This study explores the prognostic significance of tumordraining lymph nodes (TDLNs) in OSCC, with a special focus on the quantification of T regulatory cells (Tregs) and the expression of immune checkpoints on T cells.Forty-nine OSCC patients were enrolled. One TDLN per patient was analysed using flow cytometry to profile immune-checkpoint expression (PD-1, CTLA-4, TIGIT, TIM-3, LAG-3) and other markers such as CD69, CXCR5 on CD4+, CD8+, and Tregs. Disease-free survival (DFS) and overall survival (OS) were assessed.According to multivariate analysis, elevated levels of FoxP3+CD4+ and TIGIT+CD8+ cells in TDLNs correlated with significantly worse DFS, while high CXCR5+CD4+ levels were associated with better DFS. Notably, the expression of immune checkpoints on T cells within TDLNs showed significant associations with recurrence status. Patients experiencing recurrence exhibited heightened levels of T regulatory cells, CD4+PD-1+ and CD4+CTLA-4+, cells in TDLNs. Survival multivariate analyses revealed that T status emerged as an independent predictor of OS.The findings highlight the critical role of TDLNs in the immune microenvironment of OSCC and establish immune checkpoint expression on T cells as promising prognostic biomarkers.These insights upgrade the prognostic framework for OSCC and pave the way for individualized therapeutic strategies. The prognostic significance of TDLNs and a high expression of immune checkpoint inhibitors is a compelling argument for the adoption of neoadjuvant immunotherapy.

    Keywords: oral squamous cell carcinoma, tumor-draining lymph nodes, immune checkpoints, prognostic indicators, neoadjuvant immunotherapy

    Received: 26 Jun 2024; Accepted: 30 Sep 2024.

    Copyright: © 2024 Piersiala, Hjalmarsson, Lagebro, Farrajota, Bark, Elliot, Marklund, Margolin, Georen and Cardell. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Krzysztof Piersiala, Karolinska Institutet (KI), Solna, Sweden

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