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Updated: Jul 17, 2025
Intramucosal Inoculation of Squamous Cell Carcinoma Cells in Mice for Tumor Immune Profiling and Treatment Response Assessment
Published on: April 22, 2019
Genomic and Transcriptomic Landscape of an Oral Squamous Cell Carcinoma Mouse Model for Immunotherapy
Yi-Mei Lee1,2, Chia-Lang Hsu3,4, Yu-Hsin Chen1,2,4
1Department of Otolaryngology, National Taiwan University Hospital, Taipei, Taiwan.
Abstract:
The immune checkpoint inhibitor (ICI), anti-programmed death-1 (anti-PD-1), has shown moderate efficacy in some patients with head and neck squamous cell carcinoma (HNSCC). Because of this, it is imperative to establish a mouse tumor model to explore mechanisms of antitumor immunity and to develop novel therapeutic options. Here, we examined the 4-nitroquinoline-1-oxide (4NQO)-induced oral squamous cell carcinoma (OSCC) model for genetic aberrations, transcriptomic profiles, and immune cell composition at different pathologic stages. Genomic exome analysis in OSCC-bearing mice showed conservation of critical mutations found in human HNSCC. Transcriptomic data revealed that a key signature comprised of immune-related genes was increased beginning at the moderate dysplasia stages. We first identified that macrophage composition in primary tumors differed across pathologic stages, leading to an oncogenic evolution through a change in the M1/M2 macrophage ratio during tumorigenesis. We treated the 4NQO-induced OSCC-bearing mice with anti-PD-1 and agonistic anti-CD40, which modulated multiple immune responses. The growth of tumor cells was significantly decreased by agonistic anti-CD40 by promoting an increase in the M1/M2 ratio. By examining cross-species genomic conservation in human and mouse tumors, our study demonstrates the molecular mechanisms underlying the development of OSCC and the regulation of contributing immune-related factors, and aims to facilitate the development of suitable ICI-based treatments for patients with HNSCC.
Insights
This study developed a mouse model for oral squamous cell carcinoma (OSCC) to investigate antitumor immunity. The model showed conserved mutations and identified macrophage changes, aiding the development of immune checkpoint inhibitor (ICI) therapies for head and neck cancers.
Area of Science:
- Oncology
- Immunology
- Genomics
Background:
- Immune checkpoint inhibitors (ICIs) like anti-programmed death-1 (anti-PD-1) show limited efficacy in head and neck squamous cell carcinoma (HNSCC).
- Developing robust mouse models is crucial for understanding antitumor immunity and advancing therapeutic strategies for HNSCC.
Purpose of the Study:
- To establish and characterize a 4-nitroquinoline-1-oxide (4NQO)-induced oral squamous cell carcinoma (OSCC) mouse model.
- To investigate genetic aberrations, transcriptomic profiles, and immune cell composition during OSCC progression.
- To explore therapeutic interventions using anti-PD-1 and anti-CD40 in the established OSCC model.
Main Methods:
- Utilized the 4NQO-induced OSCC mouse model.
- Performed genomic exome analysis and transcriptomic profiling at various pathologic stages.
- Analyzed macrophage composition (M1/M2 ratio) and immune cell responses.
- Administered anti-PD-1 and agonistic anti-CD40 therapies to assess tumor growth inhibition.
Main Results:
- The 4NQO-induced OSCC model exhibited genetic mutations conserved in human HNSCC.
- An immune-related gene signature increased from moderate dysplasia stages.
- Macrophage composition shifted, altering the M1/M2 ratio during tumorigenesis.
- Agonistic anti-CD40 therapy significantly reduced tumor growth by increasing the M1/M2 ratio.
Conclusions:
- The 4NQO-induced OSCC mouse model effectively recapitulates key features of human HNSCC.
- Macrophage polarization is a critical factor in OSCC development and progression.
- Targeting macrophage polarization with anti-CD40 shows promise for HNSCC treatment, potentially enhancing ICI efficacy.
