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Updated: Oct 30, 2025
Intramucosal Inoculation of Squamous Cell Carcinoma Cells in Mice for Tumor Immune Profiling and Treatment Response Assessment
Published on: April 22, 2019
Explant Modeling of the Immune Environment of Head and Neck Cancer
Shay Sharon1, Thomas Duhen2, Shelly Bambina2
1Department of Oral and Maxillofacial Surgery, Hadassah and Hebrew University Medical Center, Jerusalem, Israel.
Abstract:
Patients exhibit distinct responses to immunotherapies that are thought to be linked to their tumor immune environment. However, wide variations in outcomes are also observed in patients with matched baseline tumor environments, indicating that the biological response to treatment is not currently predictable using a snapshot analysis. To investigate the relationship between the immune environment of tumors and the biological response to immunotherapies, we characterized four murine head and neck squamous cell carcinoma (HNSCC) models on two genetic backgrounds. Using tumor explants from those models, we identified correlations between the composition of infiltrating immune cells and baseline cytokine profiles prior to treatment. Following treatment with PD-1 blockade, CTLA-4 blockade, or OX40 stimulation, we observed inter-individual variability in the response to therapy between genetically identical animals bearing the same tumor. These distinct biological responses to treatment were not linked to the initial tumor immune environment, meaning that outcome would not be predictable from a baseline analysis of the tumor infiltrates. We similarly performed the explant assay on patient HNSCC tumors and found significant variability between the baseline environment of the tumors and their response to therapy. We propose that tumor explants provide a rapid biological assay to assess response to candidate immunotherapies that may allow matching therapies to individual patient tumors. Further development of explant approaches may allow screening and monitoring of treatment responses in HNSCC.
Insights
Tumor immune environments do not predict immunotherapy response. Tumor explants show variable responses, suggesting a new method for matching head and neck cancer patients to treatments.
Area of Science:
- Immunology
- Oncology
- Translational Medicine
Background:
- Patient responses to cancer immunotherapy vary widely.
- Tumor immune microenvironment is a key factor, but baseline analysis is insufficient for prediction.
- Head and neck squamous cell carcinoma (HNSCC) presents unique challenges in predicting treatment efficacy.
Purpose of the Study:
- To investigate the relationship between tumor immune environment and biological response to immunotherapy.
- To assess the predictive power of baseline tumor characteristics for immunotherapy outcomes.
- To explore the utility of tumor explants as a predictive assay for immunotherapy response.
Main Methods:
- Characterization of four murine HNSCC models on two genetic backgrounds.
- Analysis of immune cell composition and cytokine profiles in tumor explants.
- Treatment of models with PD-1 blockade, CTLA-4 blockade, and OX40 stimulation.
- Explant assay performed on patient-derived HNSCC tumors.
Main Results:
- Correlations found between baseline immune infiltrates, cytokine profiles, and tumor characteristics.
- Significant inter-individual variability in treatment response observed, even in genetically identical animals.
- Baseline tumor immune environment did not reliably predict response to immunotherapy.
- Patient HNSCC explants demonstrated variability in response to therapy.
Conclusions:
- Baseline tumor immune environment is not a sufficient predictor of immunotherapy response.
- Tumor explants offer a rapid biological assay for assessing individual patient response to immunotherapies.
- Explant approaches may enable personalized therapy selection and monitoring for HNSCC patients.
