Translational oncology · 2026
CD3 and PD-L1 tissue expression have synergistic value in head and neck squamous cell carcinoma prognosis.
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Witzleben Adrian V, Remark Romain, Idel Christian, Ribbat-Idel Julika, Krupar Rosemarie, Schröck Andreas, Klümper Niklas, Doescher Johannes, Sikora Andrew G, Kors Tsima Abou, Vahl Julius M, Brand Matthias, Sonntag Michael, Brunner Cornelia, Hoffmann Thomas K, Perner Sven, Gnjatic Sacha, Laban Simon
Аннотация
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 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.
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.