Heterogeneity of PD-L1 Expression Between the Primary Tumor and Matched Lymph Node Metastases in Head and Neck Squamous Cell Carcinomas

By M. Knebel, Gilbert Georg Klamminger, J. Kühn, S. Körner, S. Wemmert, L. Brust, F. Braun, S. Smola, Mathias Wagner, Martin Ertz and 3 more. Cancers, 2026

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Simple Summary Immunotherapy has emerged as an important treatment modality for patients with head and neck squamous cell carcinoma; however, only a minority achieve durable clinical benefit, and discordant response patterns between primary tumors and lymph node metastases have been reported. Because the use of anti-PD-1 therapy remains contingent on PD-L1 expression according to regulatory approval criteria, we investigated whether spatial heterogeneity in PD-L1 expression exists between primary tumors and matched lymph node metastases and whether such differences might contribute to variable treatment responses. Our analysis indicated that 18% of patients (CPS; 95% CI, 8.0–30.0%) exhibited discordance in PD-L1 expression between primary and metastatic sites when assessed relative to current therapeutic cut-offs. These findings highlight the potential for spatial heterogeneity in PD-L1 expression and underscore an area of uncertainty in biomarker classification. As such, they should be interpreted as hypothesis-generating. Future studies may be warranted to determine whether, and under what circumstances, reassessment of PD-L1 status in metastatic lesions—including lymph node metastases—could provide additional clinically relevant information, particularly in cases where initial testing does not meet established eligibility thresholds for anti-PD-1 therapy.

Subfields: Immunology, Oncology, Otorhinolaryngology

View Paper: https://doi.org/10.3390/cancers18081286