Longitudinal liquid biopsy identifies an early predictive biomarker of immune checkpoint blockade response in head and neck squamous cell carcinoma
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.
Authors
- Parth Desai (ORCID: https://orcid.org/0000-0002-7715-4919)
- Chi‐Ping Day (ORCID: https://orcid.org/0000-0001-5200-2372)
- Robert Saddawi‐Konefka (ORCID: https://orcid.org/0000-0002-9936-1695)
- Lauren Clubb (ORCID: https://orcid.org/0000-0003-1480-7043)
- Kun Wang (ORCID: https://orcid.org/0000-0001-8923-8557)
- Xinping Yang (ORCID: https://orcid.org/0000-0003-4086-4180)
- Sumeet Patiyal (ORCID: https://orcid.org/0000-0003-1358-292X)
- Sumit Mukherjee (ORCID: https://orcid.org/0000-0001-9807-7994)
- Eytan Ruppin (ORCID: https://orcid.org/0000-0002-7862-3940)
- Clint Allen (ORCID: https://orcid.org/0000-0001-6586-5804)
- Di Wu (ORCID: https://orcid.org/0000-0002-6241-2102)
- Saugato Rahman Dhruba (ORCID: https://orcid.org/0000-0001-5947-6757)
- Binbin Wang (ORCID: https://orcid.org/0000-0003-2885-6428)
- Shiqi Tang
- Sahil Sahni (ORCID: https://orcid.org/0009-0006-4678-3903)
- J. Silvio Gutkind
Institutions
- Fox Chase Cancer Center (US)
- The University of Texas MD Anderson Cancer Center (US)
- University of Illinois Urbana-Champaign (US)
- UC San Diego Health System (US)
- University of California San Diego (US)
- National Cancer Institute (US)
- Center for Cancer Research (US)
- Stanford University (US)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-09-01
- DOI
- https://doi.org/10.1038/s41467-025-63538-4
- Citations
- 9
- Primary Topic
- Cancer Immunotherapy and Biomarkers
- Type
- article
- Field-Weighted Citation Impact
- 9.41
Funders
- National Institutes of Health
- National Cancer Institute