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Updated: Sep 8, 2025
Monitoring PD-1-Blocking Antibodies Bound to T Cells Derived from a Drop of Peripheral Blood
Published on: February 5, 2020
Integrated peripheral blood multi-omics profiling identifies immune signatures predictive of neoadjuvant PD-1
Hao Zhang1,2,3, Wenjie Wu4, Meng Wang4
1Institute of Medical Technology, Peking University Health Science Center, Beijing, 100191, China.
Background:
Neoadjuvant 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).
Methods:
In 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.
Results:
Baseline immune profiles differed significantly between responder (RD) and non-responder (NRD): RD showed higher frequencies of CD103-CD8+ central memory T cells (Tcm, c03) and elevated plasma interleukins (IL-5, IL-13), whereas NRD had more CD28-TIGIThighcPARP-CD8+ terminally differentiated effector memory CD45RA+ T cells (Temra, c17) and higher levels of chemokines (CCL3, CCL4) and MMP7. Neoadjuvant therapy reactivated both subsets, evidenced by downregulation of PD-1 and increased expression of activation markers (e.g., CD38) and cytotoxic mediators (e.g., granzyme B and interferon γ). A multimodal predictive model incorporating CD8+T cell subsets (c03, c17) and plasma biomarkers (IL-5, MMP7) demonstrated superior predictive accuracy (AUC = 0.9219).
Conclusions:
Integrated 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 .
Insights
This study developed a liquid biopsy model to predict head and neck cancer patients' response to PD-1 inhibitor therapy. The model accurately identifies responders using immune cell profiles and plasma biomarkers, enabling personalized treatment strategies.
Area of Science:
- Immunology
- Oncology
- Proteomics
Background:
- Neoadjuvant PD-1 inhibitor therapy shows promise for locally advanced head and neck squamous cell carcinoma (HNSCC).
- However, only a subset of patients responds well to this treatment.
- Liquid biopsy offers an advantageous, non-invasive method for predicting treatment outcomes compared to traditional tissue biopsies.
Purpose of the Study:
- To develop a predictive model for neoadjuvant PD-1 therapy response in HNSCC patients.
- To utilize exclusively liquid biopsy approaches, including peripheral blood immune profiling and plasma cytokine panels.
- To enable early stratification of patients for personalized immunotherapy.
Main Methods:
- A prospective trial involving 50 HNSCC patients receiving neoadjuvant tislelizumab plus chemotherapy.
- Peripheral blood samples were analyzed pre- and post-treatment using mass cytometry (CyTOF) for immune cell subsets and Olink proteomics for plasma biomarkers.
- A multimodal predictive model was built using logistic regression.
Main Results:
- Distinct baseline immune profiles were observed between responders and non-responders.
- Responders had higher frequencies of specific CD8+ T cell subsets (c03) and elevated interleukins (IL-5, IL-13).
- A multimodal model integrating CD8+ T cell subsets (c03, c17) and plasma biomarkers (IL-5, MMP7) achieved high predictive accuracy (AUC=0.9219).
Conclusions:
- Integrated peripheral immune profiling via liquid biopsy robustly predicts neoadjuvant PD-1 blockade efficacy in HNSCC.
- Identified immune cell subsets and plasma biomarkers offer a framework for clinical decision-making and personalized immunotherapy.
- Liquid biopsy serves as a viable platform for early response stratification in HNSCC treatment.
