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<p>Most patients with relapsed or metastatic head and neck squamous cell carcinoma (rmHNSCC) do not experience durable responses to PD-1 immune checkpoint inhibitors. PD-L1 tissue expression is the most commonly assessed response marker, but an insufficient predictor of treatment outcome. To identify suitable response biomarkers, we profiled the FOCUS trial (Registered at ClinicalTrials.gov: NCT05075122) cohort for several blood- and tissue-based markers. PD-L1 levels in the tumor or tumor microenvironment were not associated with treatment benefit. In contrast, inflammation-related markers such as IL-6, sCD25, and sTIM-3, as well as high peripheral neutrophils, cell-free DNA levels, and T cell receptor repertoire clonality, were associated with poor clinical outcomes. Patients lacking these high-risk markers performed remarkably well on inhibition of immune checkpoints with pembrolizumab. Biomarker-guided patient selection for pembrolizumab monotherapy or novel combinatorial approaches—potentially including anti-inflammatory agents—for patients with immune-impaired, inflammatory profiles may be the next step in personalizing immunotherapy for these hard-to-treat patients.</p>

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Inflammation and limited adaptive immunity predict worse outcomes on immunotherapy in head and neck cancer

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年8月5日

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  • Lisa Paschold,
  • Christoph Schultheiss,
  • Paul Schmidt-Barbo,
  • Konrad Klinghammer,
  • Dennis Hahn,
  • Mareike Tometten,
  • Philippe Schafhausen,
  • Markus Blaurock,
  • Anna Brandt,
  • Ingunn Westgaard,
  • Simone Kowoll,
  • Alexander Stein,
  • Axel Hinke,
  • Mascha Binder

摘要

Most patients with relapsed or metastatic head and neck squamous cell carcinoma (rmHNSCC) do not experience durable responses to PD-1 immune checkpoint inhibitors. PD-L1 tissue expression is the most commonly assessed response marker, but an insufficient predictor of treatment outcome. To identify suitable response biomarkers, we profiled the FOCUS trial (Registered at ClinicalTrials.gov: NCT05075122) cohort for several blood- and tissue-based markers. PD-L1 levels in the tumor or tumor microenvironment were not associated with treatment benefit. In contrast, inflammation-related markers such as IL-6, sCD25, and sTIM-3, as well as high peripheral neutrophils, cell-free DNA levels, and T cell receptor repertoire clonality, were associated with poor clinical outcomes. Patients lacking these high-risk markers performed remarkably well on inhibition of immune checkpoints with pembrolizumab. Biomarker-guided patient selection for pembrolizumab monotherapy or novel combinatorial approaches—potentially including anti-inflammatory agents—for patients with immune-impaired, inflammatory profiles may be the next step in personalizing immunotherapy for these hard-to-treat patients.