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Updated: Jun 5, 2026
Intramucosal Inoculation of Squamous Cell Carcinoma Cells in Mice for Tumor Immune Profiling and Treatment Response Assessment
Published on: April 22, 2019
PARD6G mediates resistance to PD-1 immune checkpoint blockade in head and neck squamous cell carcinoma
Wei Xu1, Aibo Xu2, Xiaoting Zhang2
1School of Medical Technology and Information Engineering, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, China; Laboratory Medicine Center, Allergy Center, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, Zhejiang 310014, People's Republic of China; Key Laboratory of Precision Medicine for Head and Neck Cancers of Zhejiang Province, Zhejiang Provincial People's Hospital, Hangzhou, Zhejiang 310014, China.
Abstract:
Head and neck squamous cell carcinoma (HNSCC) remains a challenging malignancy with limited response to immune checkpoint blockade (ICB) therapies. Identifying reliable biomarkers to predict ICB response is critical for improving clinical outcomes. In this study, we identified PARD6G as a key gene associated with response to anti-PD-1 therapy in HNSCC through integrative analysis of single-cell and bulk transcriptomic data from pre- and post-treatment cohorts. Virtual PARD6G knockout modeling revealed that low PARD6G expression was associated with increased overall immune cell infiltration but significantly reduced infiltration of functional T cells. In vitro, PARD6G overexpression suppressed HNSCC cell proliferation and cell-cycle progression, while its knockdown promoted tumor growth. In vivo, PARD6G-deficient tumors exhibited accelerated growth and resistance to anti-PD-1 treatment, accompanied by a reshaped immune landscape favoring immunosuppression. In conclusion, this study establishes PARD6G as a novel predictive biomarker for anti-PD-1 efficacy and a functional tumor suppressor in HNSCC. Its loss mediates ICB resistance by reshaping the immune microenvironment, providing new insights into the mechanisms of ICB resistance in HNSCC and suggesting potential therapeutic targets.
Insights
Researchers identified PARD6G as a key gene for predicting head and neck squamous cell carcinoma response to anti-PD-1 immunotherapy. Low PARD6G expression correlates with immune evasion and resistance to treatment.
Area of Science:
- Oncology
- Immunology
- Genetics
Background:
- Head and neck squamous cell carcinoma (HNSCC) shows limited response to immune checkpoint blockade (ICB).
- Predictive biomarkers are crucial for optimizing ICB therapy in HNSCC patients.
- Understanding mechanisms of ICB resistance is vital for therapeutic advancement.
Purpose of the Study:
- To identify novel biomarkers predicting anti-PD-1 therapy response in HNSCC.
- To elucidate the functional role of PARD6G in HNSCC tumorigenesis and immune evasion.
- To investigate PARD6G's impact on the tumor immune microenvironment.
Main Methods:
- Integrative analysis of single-cell and bulk transcriptomic data from HNSCC patients pre- and post-anti-PD-1 treatment.
- Virtual PARD6G knockout modeling to assess immune cell infiltration.
- In vitro studies on HNSCC cell proliferation and cell-cycle progression.
- In vivo xenograft models to evaluate tumor growth and response to anti-PD-1 therapy.
Main Results:
- PARD6G was identified as a key gene associated with anti-PD-1 therapy response in HNSCC.
- Low PARD6G expression correlated with increased overall immune infiltration but reduced functional T cell infiltration.
- PARD6G overexpression suppressed HNSCC growth, while knockdown promoted proliferation and tumor growth.
- PARD6G-deficient tumors showed resistance to anti-PD-1 treatment and an immunosuppressive immune microenvironment.
Conclusions:
- PARD6G serves as a novel predictive biomarker for anti-PD-1 efficacy in HNSCC.
- PARD6G functions as a tumor suppressor in HNSCC, with its loss mediating ICB resistance.
- Loss of PARD6G reshapes the tumor immune microenvironment, contributing to immunotherapy resistance.
