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Updated: Aug 6, 2026
Modeling Oral-Esophageal Squamous Cell Carcinoma in 3D Organoids
Published on: December 23, 2022
Tumor microenvironment-simulated organoids for personalized therapy prediction in head and neck squamous cell
Jianguo Gan1,2, Wanrong Meng1, Fan Yang1
1State Key Laboratory of Oral Diseases, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Department of Head and Neck Oncology, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
Abstract:
Patient-derived organoids (PDOs) have emerged as promising models for predicting personalized drug responses in cancer therapy. However, the absence of essential immune and stromal components limits their ability to recapitulate the tumor microenvironment. Here, we established a total of 30 patient-derived organoids (PDOs) from 79 patients with locally advanced (LA) and recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). These PDOs maintained sustained expansion capacity and preserved the histopathological characteristics and genomic heterogeneity of their parental tumors. By integrating autologous immune cells and cancer-associated fibroblasts (CAFs) into PDOs, respectively, microenvironment-simulated PDOs (MS-PDOs) were established using a feasible co-culture condition. Compared with conventional PDOs, MS-PDOs-PBMC exhibited specific cytotoxicity and responses to PD-1/PD-L1 inhibitors, while MS-PDOs-CAFs showed enhanced tolerance to chemotherapy drugs, indicating that microenvironment components modulate therapeutic responses in HNSCC. The drug response profiles of MS-PDOs exhibited diverse sensitivity to PD-1/PD-L1 inhibitors, chemotherapy drugs, and combination regimens. Notably, the therapeutic predictions of MS-PDOs were consistent with clinical treatment outcomes, supporting their translational relevance. Collectively, MS-PDOs serve as a robust platform for modeling the tumor microenvironment and predicting therapeutic responses, supporting precision medicine-guided clinical decision-making and offering personalized treatment strategies for HNSCC patients.
Insights
Patient-derived organoids (PDOs) were enhanced to simulate the tumor microenvironment (MS-PDOs) for predicting head and neck cancer drug responses. These models accurately reflect patient outcomes, advancing personalized cancer therapy.
Area of Science:
- Oncology
- Cancer Biology
- Drug Discovery
Background:
- Patient-derived organoids (PDOs) are valuable for personalized cancer therapy but lack tumor microenvironment components.
- Accurately modeling the tumor microenvironment is crucial for predicting drug efficacy in head and neck squamous cell carcinoma (HNSCC).
Purpose of the Study:
- To establish microenvironment-simulated PDOs (MS-PDOs) by incorporating immune cells and cancer-associated fibroblasts (CAFs).
- To evaluate the impact of microenvironment components on therapeutic responses in HNSCC models.
- To validate MS-PDOs as predictive models for clinical treatment outcomes in HNSCC.
Main Methods:
- Developed 30 PDOs from 79 locally advanced (LA) and recurrent/metastatic (R/M) HNSCC patients.
- Co-cultured PDOs with autologous peripheral blood mononuclear cells (PBMCs) and CAFs to create MS-PDOs.
- Assessed cytotoxicity and drug responses to immunotherapy (PD-1/PD-L1 inhibitors) and chemotherapy in MS-PDOs.
Main Results:
- MS-PDOs with PBMCs showed specific responses to PD-1/PD-L1 inhibitors.
- MS-PDOs with CAFs demonstrated altered tolerance to chemotherapy.
- Drug response predictions from MS-PDOs correlated with clinical treatment outcomes in HNSCC patients.
Conclusions:
- MS-PDOs effectively model the HNSCC tumor microenvironment and modulate therapeutic responses.
- MS-PDOs provide a robust platform for predicting personalized drug efficacy.
- This approach supports precision medicine and guides clinical decision-making for HNSCC treatment.
