Schweihofer, Verena and Schulz, Daniela and Blazquez, Raquel and Brockhoff, Gero and Ettl, Tobias and Fiedler, Mathias and Heimer, Sina and Schikora, Juliane and Bauer, Richard J. and Wege, Anja Kathrin (2025) Multiplexed immune profiling and 3D co-culture assays to assess the individual checkpoint therapy response in head and neck squamous cell carcinoma. FRONTIERS IN ONCOLOGY, 15: 1622008. ISSN 2234-943X,
Full text not available from this repository. (Request a copy)Abstract
Background Immune checkpoint inhibitors (ICIs) have become an integral part of cancer therapy, but only a minority of patients experience durable responsiveness. Response rates vary greatly and are often unpredictable, highlighting the urgent need for predictive biomarkers to guide treatment decisions.Methods We investigated immune- and tumor-specific expression and secretion profiles in peripheral blood and tumor samples derived from patients with head and neck squamous cell carcinoma (HNSCC). We combined flow cytometry, LEGENDplex (TM) immune profiling, and preoperative/postoperative serum cytokine analyses to determine checkpoint molecules (e.g., PD-1, TIM-3, LAG-3), immune cell profiles, as well as key markers on tumor cells (CD44, PD-L1, MHC class I/II). In addition, a 3D co-culture model using tumor slices and autologous mononuclear cells from selected HNSCC patients were analyzed upon atezolizumab and pembrolizumab treatment.Results Co-expression of PD-1 and TIM-3 on a subset of CD8+ tumor-infiltrating T cells was frequently observed, alongside a pronounced infiltration of myeloid cells in the tumor microenvironment. In the peripheral blood, we detected elevated levels of soluble CD27 in patients compared to controls and distinct preoperative cytokine profiles (e.g., reduced IFN-gamma, CCL3, CCL20; elevated IL-15/IL-16). Postoperatively, most cytokines showed lower levels compared to healthy controls but significantly higher CCL2 levels. Furthermore, tumor-immune co-cultures from selected patients showed a stronger apoptotic response and phenotypic differences (e.g., increased PD-1 and CD137 expression) upon atezolizumab treatment. Individual changes in soluble factor release (e.g., Gal-9, sPD-L1, sCD25, and sTIM-3) was noticeable upon co-culture under immune checkpoint therapy.Conclusions This study provides proof-of-principle data suggesting that a combined multiplexed marker profiling and a functional 3D co-culture assay may help to explore predictive ICI response for HNSCC patients in the future. However, extensive studies with larger cohorts are warranted to validate and refine this approach.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | CANCER STEM-CELL; PD-L1 EXPRESSION; TUMOR; IMMUNOTHERAPY; PEMBROLIZUMAB; PROGRESSION; RECURRENT; PATHWAYS; CULTURE; LABEL; head and neck squamous cell carcinoma (HNSCC); immune checkpoint inhibitors (ICI); tumor microenvironment (TME); multiplexed immune profiling; (patient-derived) organotypic slice co-culture; predictive biomarkers; <italic>ex vivo</italic> culture model; precision oncology |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Dermatologie und Venerologie Medicine > Lehrstuhl für Frauenheilkunde und Geburtshilfe (Schwerpunkt Frauenheilkunde) Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie) Medicine > Lehrstuhl für Mund-, Kiefer- und Gesichtschirurgie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 16 Jun 2026 05:23 |
| Last Modified: | 16 Jun 2026 05:23 |
| URI: | https://pred.uni-regensburg.de/id/eprint/65952 |
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