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Updated: Aug 6, 2025
Therapy Testing in a Spheroid-based 3D Cell Culture Model for Head and Neck Squamous Cell Carcinoma
Published on: April 20, 2018
Exploration of prognostic biomarkers in head and neck squamous cell carcinoma microenvironment from TCGA database
Ying Li1, Jianping Bi1, Guoliang Pi1
1Department of Radiation Oncology, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Background:
Immune checkpoint blockade (ICB) therapies have redefined human cancer treatment, including for head and neck squamous cell carcinoma (HNSCC). However, clinical responses to various immune checkpoint inhibitors are often accompanied by immune-related adverse events (irAEs). Therefore, it is crucial to obtain a comprehensive understanding of the association between different immune tumor microenvironments (TMEs) and the immunotherapeutic response.
Methods:
The research data were obtained from The Cancer Genome Atlas (TCGA) database. We applied RNA-seq genomic data from tumor biopsies to assess the immune TME in HNSCC. As the TME is a heterogeneous system that is highly associated with HNSCC progression and clinical outcome, we relied on the Estimation of Stromal and Immune cells in Malignant Tumor tissues using Expression data (ESTIMATE) algorithm to calculate immune and stromal scores that were evaluated based on the immune or stromal components in the TME. Then, the Tumor Immune Dysfunction and Exclusion algorithm (TIDE) was used to predict the benefits of ICB to each patient. Finally, we identified specific prognostic tumor-infiltrating immune cells (TIICs) by quantifying the cellular composition of the immune response in HNSCC and its association to survival outcome, using the CIBERSORT algorithm.
Results:
Utilizing the HNSCC cohort of the TCGA database and TIDE and ESTIMATE algorithm-derived immune scores, we obtained a list of microenvironment-associated lncRNAs that predicted different clinical outcomes in HNSCC patients. We validated these correlations in a different HNSCC cohort available from the TCGA database and provided insight into the prediction of response to ICB therapies in HNSCC.
Conclusions:
This study confirmed that CD8+ T cells were significantly associated with better survival in HNSCC and verified that the top five significantly mutated genes (SMGs) in the TCGA HNSCC cohort were TP53, TTN, FAT1, CDKN2A, and MUC16. A high level of CD8+ T cells and high immune and stroma scores corresponded to a better survival probability in HNSCC.
Insights
This study reveals that higher CD8+ T cell levels and immune scores in head and neck squamous cell carcinoma (HNSCC) correlate with improved survival. Understanding the tumor microenvironment (TME) is key for predicting immunotherapy response.
Area of Science:
- Oncology
- Immunology
- Genomics
Background:
- Immune checkpoint blockade (ICB) therapies have advanced cancer treatment, including for head and neck squamous cell carcinoma (HNSCC).
- Immune-related adverse events (irAEs) are common with ICB, necessitating a deeper understanding of the tumor microenvironment (TME) and its link to treatment efficacy.
- Investigating the TME's role is crucial for optimizing ICB strategies and predicting patient responses.
Purpose of the Study:
- To analyze the immune TME in HNSCC using RNA-seq data from The Cancer Genome Atlas (TCGA).
- To identify associations between TME characteristics, specific immune cells, and clinical outcomes in HNSCC patients.
- To predict the efficacy of ICB therapies based on TME composition and associated molecular markers.
Main Methods:
- Utilized RNA-seq data from the TCGA HNSCC cohort.
- Applied the Estimation of Stromal and Immune cells in Malignant Tumor tissues using Expression data (ESTIMATE) algorithm to calculate immune and stromal scores.
- Employed the Tumor Immune Dysfunction and Exclusion (TIDE) algorithm for ICB response prediction and CIBERSORT for quantifying tumor-infiltrating immune cells (TIICs).
Main Results:
- Identified microenvironment-associated lncRNAs that predict distinct clinical outcomes in HNSCC.
- Validated these findings in an independent TCGA HNSCC cohort, providing insights into ICB response prediction.
- Confirmed a significant association between high CD8+ T cell infiltration and better survival in HNSCC patients.
Conclusions:
- High levels of CD8+ T cells, along with elevated immune and stroma scores, are linked to improved survival probability in HNSCC.
- The study identified key significantly mutated genes (SMGs) in HNSCC, including TP53, TTN, FAT1, CDKN2A, and MUC16.
- These findings enhance our understanding of the HNSCC TME and its implications for immunotherapy response and patient prognosis.
