CD3 and PD-L1 tissue expression have synergistic value in head and neck squamous cell carcinoma prognosis

  • Introduction T cell infiltrates, particularly CD3+ T cells, have been linked to a favorable prognosis in cancer. However, the influence of PD-L1 expression on survival remains controversial, particularly in patients who do not receive immune checkpoint inhibition. This goal of this study was to combine CD3 density and PD-L1 expression to assess their individual and combined prognostic value in head and neck squamous cell carcinoma (HNSCC) patients treated with surgery and adjuvant therapy. Materials and Methods A tissue microarray of 458 HNSCC primary tumor samples was analyzed for CD3 and PD-L1 expression using multiplex immunohistochemistry. CD3 densities were quantified using digital image analysis (QuPath), and PD-L1 expression was categorized by the Combined Positive Score (CPS). Overall survival (OS) and recurrence-free survival (RFS) were calculated and compared across different expression profiles using the Kaplan-Meier method followed by a multivariate cox regressionIntroduction T cell infiltrates, particularly CD3+ T cells, have been linked to a favorable prognosis in cancer. However, the influence of PD-L1 expression on survival remains controversial, particularly in patients who do not receive immune checkpoint inhibition. This goal of this study was to combine CD3 density and PD-L1 expression to assess their individual and combined prognostic value in head and neck squamous cell carcinoma (HNSCC) patients treated with surgery and adjuvant therapy. Materials and Methods A tissue microarray of 458 HNSCC primary tumor samples was analyzed for CD3 and PD-L1 expression using multiplex immunohistochemistry. CD3 densities were quantified using digital image analysis (QuPath), and PD-L1 expression was categorized by the Combined Positive Score (CPS). Overall survival (OS) and recurrence-free survival (RFS) were calculated and compared across different expression profiles using the Kaplan-Meier method followed by a multivariate cox regression analysis. Results CD3high tumors (defined as greater the median CD3 expression) were associated with longer OS and RFS compared to CD3low tumors (below median). Similarly, PD-L1 expression at CPS ≥ 1 was linked to significantly better survival outcomes than CPS < 1. The combination of CD3high and PD-L1 CPS ≥ 1 showed the most favorable prognosis. Conclusion The combined assessment of CD3 density and PD-L1 expression outperforms either marker alone in predicting survival outcomes in surgically treated patients without immunotherapy. CD3high and PD-L1 CPS ≥ 1 identifies patients with favorable prognosis and response to standard-of-care treatment. Nonetheless, the potential relevance of these markers for guiding immunotherapy in other setting remains to be explored.show moreshow less

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Metadaten
Author:Adrian von Witzleben, Romain Remark, Christian Idel, Julika Ribbat-Idel, Rosemarie Krupar, Andreas Schröck, Niklas Klümper, Johannes DoescherORCiDGND, Andrew G. Sikora, Tsima Abou Kors, Julius M. Vahl, Matthias Brand, Michael Sonntag, Cornelia Brunner, Thomas K. Hoffmann, Sven Perner, Sacha Gnjatic, Simon Laban
URN:urn:nbn:de:bvb:384-opus4-1298549
Frontdoor URLhttps://opus.bibliothek.uni-augsburg.de/opus4/129854
ISSN:1936-5233OPAC
Parent Title (English):Translational Oncology
Publisher:Elsevier BV
Place of publication:Amsterdam
Type:Article
Language:English
Year of first Publication:2026
Publishing Institution:Universität Augsburg
Release Date:2026/04/27
Volume:68
First Page:102776
DOI:https://doi.org/10.1016/j.tranon.2026.102776
Institutes:Medizinische Fakultät
Medizinische Fakultät / Universitätsklinikum
Medizinische Fakultät / Lehrstuhl für Hals-, Nasen- und Ohrenheilkunde
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):CC-BY 4.0: Creative Commons: Namensnennung