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Updated: Oct 15, 2025
Isolation and Characterization of a Head and Neck Squamous Cell Carcinoma Subpopulation Having Stem Cell Characteristics
Published on: May 11, 2016
Targeting LSD1 suppresses stem cell-like properties and sensitizes head and neck squamous cell carcinoma to PD-1
Yong Han1,2,3,4, Shengming Xu1,2,3,4, Weimin Ye1,2,3,4
1Department of Oral and Maxillofacial-Head and Neck Oncology, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Abstract:
Head and neck squamous cell carcinoma (HNSCC) is a highly aggressive tumor with poor clinical outcomes due to recurrence, metastasis, and treatment resistance. Cancer stem cells (CSCs), a small population among tumor cells, are proposed to be responsible for tumor initiation, progression, metastasis, drug resistance, and recurrence. Here we show that high LSD1 expression was a predictor of poor prognosis for HNSCC patients. We found that high expression of LSD1 is essential for the maintenance of the CSC properties by regulating Bmi-1 expression. Moreover, tumor LSD1 ablation suppresses CSC-like characteristics in vitro and inhibits tumorigenicity in vivo in immune-deficient xenografts. However, this deletion induces the upregulation of PDL1 levels, which compromises antitumor immunity and reduces antitumor efficacy in an immune-competent mouse model. Functionally, the combination of LSD1 inhibitor and anti-PD-1 monoclonal antibody can overcome tumor immune evasion and greatly inhibit tumor growth, which was associated with reduced Ki-67 level and augmented CD8+ T cell infiltration in immunocompetent tumor-bearing mouse models. In summary, these findings provide a novel and promising combined strategy for the treatment of HNSCC using a combination of LSD1 inhibition and PD-1 blockade.
Insights
High lysine-specific demethylase 1 (LSD1) expression drives head and neck squamous cell carcinoma (HNSCC) progression and resistance. Combining LSD1 inhibitors with PD-1 blockade offers a promising new strategy to overcome immune evasion and treat HNSCC.
Area of Science:
- Oncology
- Cancer Stem Cell Biology
- Immunotherapy
Background:
- Head and neck squamous cell carcinoma (HNSCC) is aggressive, characterized by recurrence, metastasis, and treatment resistance.
- Cancer stem cells (CSCs) are implicated in HNSCC initiation, progression, metastasis, drug resistance, and recurrence.
- High expression of lysine-specific demethylase 1 (LSD1) is linked to poor prognosis in HNSCC patients.
Purpose of the Study:
- To investigate the role of LSD1 in maintaining CSC properties in HNSCC.
- To evaluate the therapeutic potential of LSD1 inhibition and PD-1 blockade in HNSCC treatment.
Main Methods:
- Assessed LSD1 expression as a prognostic marker in HNSCC patients.
- Investigated LSD1's role in CSC maintenance by regulating Bmi-1 expression.
- Utilized tumor LSD1 ablation in vitro and in vivo (xenografts and immunocompetent models).
- Evaluated the combination therapy of LSD1 inhibitor and anti-PD-1 antibody in mouse models.
Main Results:
- High LSD1 expression correlates with poor prognosis in HNSCC.
- LSD1 is essential for CSC maintenance via Bmi-1 regulation; its ablation suppresses CSC traits and tumorigenicity.
- LSD1 ablation upregulates PDL1, compromising antitumor immunity.
- Combined LSD1 inhibition and PD-1 blockade effectively inhibit tumor growth by reducing proliferation (Ki-67) and increasing CD8+ T cell infiltration.
Conclusions:
- LSD1 plays a critical role in HNSCC progression and CSC maintenance.
- Targeting LSD1 can suppress tumor growth but may induce immune evasion.
- Combination therapy with LSD1 inhibitors and PD-1 blockade presents a novel and effective strategy for HNSCC treatment.
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