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

作者：Binbin Wang, Robert Saddawi‐Konefka, Lauren Clubb, Shiqi Tang, Di Wu, Sumit Mukherjee, Sahil Sahni, Saugato Rahman Dhruba, Xinping Yang, Sumeet Patiyal, Chi‐Ping Day, Parth Desai, Clint Allen, Kun Wang, J. Silvio Gutkind, Eytan Ruppin · 发表于：Nature Communications · 年份：2025 · DOI：10.1038/s41467-025-63538-4 · 被引用次数：14 · 研究领域：Cancer Immunotherapy and Biomarkers、Cancer Genomics and Diagnostics、Single-cell and spatial transcriptomics

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.