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<p>Immune checkpoint blockade (ICB) has improved outcomes for patients with head and neck squamous cell carcinoma (HNSCC), but predictive biomarkers remain limited. Here, we use a time-resolved, multi-omic approach in a murine HNSCC model to characterize peripheral immune responses to ICB. Single-cell transcriptomics and T/B cell receptor analyses&#xa0; reveal early on-treatment expansion of effector memory T and B cell repertoires in responders, preceding tumor regression. These dynamic immune features inform a composite transcriptional signature that accurately predicts ICB response in independent human HNSCC cohorts. LiBIO outperforms existing biomarkers and generalizes to melanoma, non-small cell lung cancer, and breast cancer without retraining. These findings suggest that early treatment-induced changes in circulating immune repertoires reflect the host’s capacity to mount an effective antitumor response. This work provides a framework for leveraging transient peripheral immune dynamics to develop non-invasive, high-fidelity biomarkers for response to immunotherapy across cancer types.</p>

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Longitudinal liquid biopsy identifies an early predictive biomarker of immune checkpoint blockade response in head and neck squamous cell carcinoma

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年9月1日

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  • Binbin Wang,
  • Robert Saddawi-Konefka,
  • Lauren M. Clubb,
  • Shiqi Tang,
  • Di Wu,
  • Sumit Mukherjee,
  • Sahil Sahni,
  • Saugato Rahman Dhruba,
  • Xinping Yang,
  • Sumeet Patiyal,
  • Chi-Ping Day,
  • Parth A. Desai,
  • Clint Allen,
  • Kun Wang,
  • J. Silvio Gutkind,
  • Eytan Ruppin

摘要

Immune checkpoint blockade (ICB) has improved outcomes for patients with head and neck squamous cell carcinoma (HNSCC), but predictive biomarkers remain limited. Here, we use a time-resolved, multi-omic approach in a murine HNSCC model to characterize peripheral immune responses to ICB. Single-cell transcriptomics and T/B cell receptor analyses  reveal early on-treatment expansion of effector memory T and B cell repertoires in responders, preceding tumor regression. These dynamic immune features inform a composite transcriptional signature that accurately predicts ICB response in independent human HNSCC cohorts. LiBIO outperforms existing biomarkers and generalizes to melanoma, non-small cell lung cancer, and breast cancer without retraining. These findings suggest that early treatment-induced changes in circulating immune repertoires reflect the host’s capacity to mount an effective antitumor response. This work provides a framework for leveraging transient peripheral immune dynamics to develop non-invasive, high-fidelity biomarkers for response to immunotherapy across cancer types.