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<p>Programmed cell death protein-1 (PD-1)/programmed cell death ligand 1 (PD-L1) blockade is the standard therapy for recurrent or metastatic head and neck squamous cell carcinoma (RMHNSCC), yet many patients exhibit poor responses. Potential non-invasive biomarkers for predicting treatment response in RMHNSCC remain unclear. In this study, we collected blood samples from 47 RMHNSCC patients and 17 healthy controls. PD-1 expression was evaluated using 10-color flow cytometry before treatment. Subpopulations of peripheral blood lymphocytes (PBLs) were assessed at baseline, 2–3 weeks, and 6 weeks after the first anti-PD-1 immune checkpoint inhibitor (ICI) treatment. A total of 116 patient samples were used for longitudinal comparison of treatment-induced changes in lymphocyte subpopulations. Patients had higher PD-1+ PBL levels than healthy individuals (25.0% vs. 20.3%, <i>P</i> = 0.006). Those with PD-1+ PBLs ≥ 25% exhibited elevated T cell levels and higher frequencies of PD-1+lymphocyte subsets expressing CD38 and HLA-DR concurrently or CD56/CD16, alongside reduced NK cell levels before anti-PD1 therapy. The median progression-free survival (PFS) was 2.2 months, with an overall one-year PFS rate of 18%. The patients with PD-1+ PBLs ≥ 25% showed significantly poorer one-year PFS (7% vs. 29%, <i>P</i> = 0.039) and overall survival rates (20% vs. 50%, <i>P</i> = 0.018) than the opposite group. Comparing fold changes from baseline, the patients with PD-1+PBLs ≥ 25% showed significantly lower increases in CD4+CD38+HLA-DR +T cells (median: 1.15 vs. 1.66 at the first post-treatment test), and CD8+CD38 + HLA-DR + T cells (medians: 1.01 vs. 1.34 and 1.23 vs. 1.78 at the first and second post-treatment tests, respectively) compared to the opposing group. Our findings indicate that high PD-1 expression in PBLs predicts poor treatment outcomes for anti-PD-1 ICIs in patients with RMHNSCC. Dynamic immune monitoring can assist physicians in tailoring personalized therapeutic strategies.</p>

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High PD-1 expression in pre-treatment peripheral lymphocytes associated with poor immune checkpoint inhibitor response in patients with recurrent or metastatic head and neck squamous cell carcinoma

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年2月7日

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  • Shau-Hsuan Li,
  • Wan-Ting Huang

摘要

Programmed cell death protein-1 (PD-1)/programmed cell death ligand 1 (PD-L1) blockade is the standard therapy for recurrent or metastatic head and neck squamous cell carcinoma (RMHNSCC), yet many patients exhibit poor responses. Potential non-invasive biomarkers for predicting treatment response in RMHNSCC remain unclear. In this study, we collected blood samples from 47 RMHNSCC patients and 17 healthy controls. PD-1 expression was evaluated using 10-color flow cytometry before treatment. Subpopulations of peripheral blood lymphocytes (PBLs) were assessed at baseline, 2–3 weeks, and 6 weeks after the first anti-PD-1 immune checkpoint inhibitor (ICI) treatment. A total of 116 patient samples were used for longitudinal comparison of treatment-induced changes in lymphocyte subpopulations. Patients had higher PD-1+ PBL levels than healthy individuals (25.0% vs. 20.3%, P = 0.006). Those with PD-1+ PBLs ≥ 25% exhibited elevated T cell levels and higher frequencies of PD-1+lymphocyte subsets expressing CD38 and HLA-DR concurrently or CD56/CD16, alongside reduced NK cell levels before anti-PD1 therapy. The median progression-free survival (PFS) was 2.2 months, with an overall one-year PFS rate of 18%. The patients with PD-1+ PBLs ≥ 25% showed significantly poorer one-year PFS (7% vs. 29%, P = 0.039) and overall survival rates (20% vs. 50%, P = 0.018) than the opposite group. Comparing fold changes from baseline, the patients with PD-1+PBLs ≥ 25% showed significantly lower increases in CD4+CD38+HLA-DR +T cells (median: 1.15 vs. 1.66 at the first post-treatment test), and CD8+CD38 + HLA-DR + T cells (medians: 1.01 vs. 1.34 and 1.23 vs. 1.78 at the first and second post-treatment tests, respectively) compared to the opposing group. Our findings indicate that high PD-1 expression in PBLs predicts poor treatment outcomes for anti-PD-1 ICIs in patients with RMHNSCC. Dynamic immune monitoring can assist physicians in tailoring personalized therapeutic strategies.