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Intramucosal Inoculation of Squamous Cell Carcinoma Cells in Mice for Tumor Immune Profiling and Treatment Response Assessment
Published on: April 22, 2019
Effect of PTEN Overexpression Plus Anti-PD-1 on Immune Escape in Oral Squamous Cell Carcinoma
Jiaxin Luo1, Yang Yang1, Yuanyang Li1
1Department of Oral and Maxillofacial Surgery, The Affiliated Stomatological Hospital, Southwest Medical University, Luzhou, China.
Objectives:
Phosphatase and tensin homolog (PTEN) is an essential regulator of tumor proliferation, apoptosis, and migration. However, the mechanisms by which PTEN regulates immune escape and its implications in immune checkpoint inhibitor combination therapy in oral squamous cell carcinoma (OSCC) remain unclear.
Methods:
We analyzed the expression of PTEN and PD-L1 in OSCC tissues and cell lines, and their associations with clinicopathological characteristics. The role of PTEN in modulating PD-L1 expression and facilitating tumor immune evasion was investigated using western blotting and T-cell cytotoxicity assays. PTEN regulation efficacy, alone or with immune checkpoint inhibitors, was evaluated in humanized xenograft mice.
Results:
Reduced PTEN and increased PD-L1 were strongly correlated with high clinical stage, positive lymph node metastasis, and lower CD8+ T-cell infiltration. Patients with lower PTEN, higher PD-L1, higher clinical stage, and positive lymph node metastasis experienced shorter overall survival. PTEN overexpression suppressed PD-L1 levels and promoted cytotoxic T-cell activity in OSCC cells by inhibiting PI3K/AKT signaling in vitro. Upregulating PTEN alone or combined with anti-PD-1 treatment effectively inhibited OSCC tumor progression and promoted CD8+ T-cell infiltration in tumors in vivo.
Conclusions:
PTEN upregulation enhances the antitumor immune response of CD8+ T-cells, suggesting a potential OSCC immunotherapy strategy.
Insights
Restoring Phosphatase and tensin homolog (PTEN) in oral squamous cell carcinoma (OSCC) boosts CD8+ T-cell immunity. This suggests PTEN upregulation is a promising immunotherapy strategy for OSCC, potentially improving patient outcomes.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- Phosphatase and tensin homolog (PTEN) is a key regulator of tumor cell behavior, including proliferation, apoptosis, and migration.
- The role of PTEN in immune evasion and its potential in combination immunotherapy for oral squamous cell carcinoma (OSCC) is not well understood.
Purpose of the Study:
- To investigate the mechanisms by which PTEN influences immune escape in OSCC.
- To evaluate the efficacy of PTEN modulation in combination with immune checkpoint inhibitors for OSCC treatment.
Main Methods:
- Analysis of PTEN and PD-L1 expression in OSCC tissues and cell lines.
- Western blotting and T-cell cytotoxicity assays to assess PTEN's role in PD-L1 regulation and immune evasion.
- In vivo studies using humanized xenograft mice to evaluate PTEN-based therapies, alone and with immune checkpoint inhibitors.
Main Results:
- Reduced PTEN and elevated PD-L1 expression correlated with advanced clinical stage, lymph node metastasis, and decreased CD8+ T-cell infiltration in OSCC.
- Lower PTEN and higher PD-L1 levels were associated with poorer patient survival.
- PTEN overexpression inhibited PI3K/AKT signaling, suppressed PD-L1, and enhanced cytotoxic T-cell activity in vitro.
- Upregulating PTEN, alone or with anti-PD-1 therapy, reduced tumor progression and increased CD8+ T-cell infiltration in vivo.
Conclusions:
- PTEN upregulation enhances the antitumor immune response mediated by CD8+ T-cells.
- Modulating PTEN presents a potential immunotherapy strategy for oral squamous cell carcinoma.
