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Updated: Jul 28, 2025
Isolation and Characterization of a Head and Neck Squamous Cell Carcinoma Subpopulation Having Stem Cell Characteristics
Published on: May 11, 2016
A novel autophagy-related subtypes to distinguish immune phenotypes and predict immunotherapy response in head and
Bo Ma1, Hui Li1, Mingzhu Zheng1
1Department of Stomatology, Beijing Shijitan Hospital, Capital Medical University, Beijing, China.
Abstract:
Both the absence of autophagy and excessive autophagy is double-edged sword in tumorigenesis. Due to the specificity of autophagy, its role in head and neck squamous cell carcinoma (HNSCC) is still unclear. In this study, we established five autophagy-related patterns in 1165 HNSCC patients with distinct cellular and molecular characteristics. Additionally, we developed a new scoring system (ATPscore) based on the differentially expressed genes (DEGs) among these five patterns, to represent the individual autophagy regulation pattern. ATPscore was shown to be significantly correlated with tumor immune microenvironment (TIME) infiltration, immune phenotypes, molecular subtypes, and genetic variations. We further found that ATPscore was both an independent prognostic factor and a potent predictor of clinical response to immune-checkpoint inhibitors (ICIs) based immunotherapy. We further verified the value of key gene SRPX in ATPscore in HNSCC cell lines with the in-depth research of ATPscore and found that it is closely related to immune subtypes, molecular subtypes, and immune activation-related markers. Our research could help us to understand the underlying mechanisms of tumor immunity and provide a solid foundation for combination of autophagy-targeted therapies with immunotherapies for clinical application in HNSCC.
Insights
Autophagy
Area of Science:
- Oncology
- Cell Biology
- Immunology
Background:
- Autophagy's role in cancer is complex, acting as a double-edged sword in tumorigenesis.
- Its specific function in head and neck squamous cell carcinoma (HNSCC) remains largely undefined.
- Understanding autophagy regulation is crucial for developing effective cancer therapies.
Purpose of the Study:
- To define distinct autophagy-related patterns in HNSCC.
- To develop a novel scoring system (ATPscore) for individual autophagy regulation.
- To investigate the correlation of ATPscore with tumor characteristics and treatment response.
Main Methods:
- Clustering 1165 HNSCC patients into five autophagy-related patterns.
- Developing the ATPscore based on differentially expressed genes (DEGs) across patterns.
- Analyzing correlations between ATPscore, tumor immune microenvironment (TIME), molecular subtypes, and genetic variations.
Main Results:
- ATPscore significantly correlates with TIME infiltration, immune phenotypes, molecular subtypes, and genetic variations.
- ATPscore serves as an independent prognostic factor for HNSCC patients.
- ATPscore predicts clinical response to immune-checkpoint inhibitors (ICIs) in HNSCC.
Conclusions:
- The developed ATPscore effectively characterizes individual autophagy regulation in HNSCC.
- ATPscore provides insights into tumor immunity and potential therapeutic strategies.
- This research lays the groundwork for combining autophagy-targeted therapies with immunotherapies in HNSCC.
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