Integrated peripheral blood multi-omics profiling identifies immune signatures predictive of neoadjuvant PD-1 blockade efficacy in head and neck squamous cell carcinoma.

backgroundNeoadjuvant PD-1 inhibitor therapy has shown promise in locally advanced head and neck squamous cell carcinoma (HNSCC), but only a subset of patients achieves major pathological responses. Liquid biopsy, the analysis of tumor-derived biomarkers in readily accessible bodily fluids (primarily blood), offers significant advantages over traditional tissue biopsies for predicting cancer treatment outcomes. The aim of this study is to develop a predictive model for neoadjuvant PD-1 therapy response in HNSCC patients using exclusively liquid biopsy approaches-namely, peripheral blood immune profiling (CyTOF) and plasma cytokine panels (Olink).

methodsIn a prospective trial involving 50 HNSCC patients treated with neoadjuvant tislelizumab plus chemotherapy, peripheral blood samples were collected pre- and post-treatment. Immune cell subsets were analyzed by mass cytometry (CyTOF), and circulating protein markers were quantified via a 92-plex targeted proteomics panel (Olink). Multimodal features were integrated into a predictive model using logistic regression.

resultsBaseline immune profiles differed significantly between responder (RD) and non-responder (NRD): RD showed higher frequencies of CD103

conclusionsIntegrated peripheral immune profiling enables robust, noninvasive prediction of neoadjuvant PD-1 blockade efficacy in HNSCC. The identified immune cell subsets and plasma biomarkers provide a clinically applicable framework for early response stratification and personalized immunotherapy, supporting liquid biopsy as a viable platform for clinical decision-making. Trial registration Chinese Clinical Trial Registry, clinical trial number CHiCTR2200056354, 04 February 2022, https://www.chictr.org.cn/showproj.html?proj=151364 .