Longitudinal liquid biopsy identifies an early predictive biomarker of immune checkpoint blockade response in head and neck squamous cell carcinoma
- 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
2025-09-01
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.