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Updated: Jul 6, 2025
Intramucosal Inoculation of Squamous Cell Carcinoma Cells in Mice for Tumor Immune Profiling and Treatment Response Assessment
Published on: April 22, 2019
AIM2 promotes irradiation resistance, migration ability and PD-L1 expression through STAT1/NF-κB activation in oral
Hui-Wen Chiu1,2,3, Hsin-Lun Lee4,5, Hsun-Hua Lee6,7,8
1Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, 11031, Taiwan.
Background:
Radioresistance and lymph node metastasis are common phenotypes of refractory oral squamous cell carcinoma (OSCC). As a result, understanding the mechanism for radioresistance and metastatic progression is urgently needed for the precise management of refractory OSCC. Recently, immunotherapies, e.g. immune checkpoint inhibitors (ICIs), were employed to treat refractory OSCC; however, the lack of predictive biomarkers still limited their therapeutic effectiveness.
Methods:
The Cancer Genome Atlas (TCGA)/Gene Expression Omnibus (GEO) databases and RT-PCR analysis were used to determine absent in melanoma 2 (AIM2) expression in OSCC samples. Colony-forming assay and trans-well cultivation was established for estimating AIM2 function in modulating the irradiation resistance and migration ability of OSCC cells, respectively. RT-PCR, Western blot and flow-cytometric analyses were performed to examine AIM2 effects on the expression of programmed death-ligand 1 (PD-L1) expression. Luciferase-based reporter assay and site-directed mutagenesis were employed to determine the transcriptional regulatory activity of Signal Transducer and Activator of Transcription 1 (STAT1) and NF-κB towards the AIM2-triggered PD-L1 expression.
Results:
Here, we found that AIM2 is extensively upregulated in primary tumors compared to the normal adjacent tissues and acts as a poor prognostic marker in OSCC. AIM2 knockdown mitigated, but overexpression promoted, radioresistance, migration and PD-L1 expression via modulating the activity of STAT1/NF-κB in OSCC cell variants. AIM2 upregulation significantly predicted a favorable response in patients receiving ICI treatments.
Conclusions:
Our data unveil AIM2 as a critical factor for promoting radioresistance, metastasis and PD-L1 expression and as a potential biomarker for predicting ICI effectiveness on the refractory OSCC.
Insights
Absent in melanoma 2 (AIM2) promotes radioresistance and metastasis in oral squamous cell carcinoma (OSCC). Upregulated AIM2 predicts a better response to immune checkpoint inhibitors (ICIs) in refractory OSCC patients.
Area of Science:
- Oncology
- Molecular Biology
- Immunotherapy
Background:
- Refractory oral squamous cell carcinoma (OSCC) presents challenges due to radioresistance and metastasis.
- Understanding mechanisms driving these phenotypes is crucial for effective OSCC management.
- Immune checkpoint inhibitors (ICIs) show promise but lack predictive biomarkers.
Purpose of the Study:
- To investigate the role of absent in melanoma 2 (AIM2) in OSCC radioresistance, metastasis, and response to immunotherapy.
- To identify AIM2 as a potential predictive biomarker for ICI treatment effectiveness in OSCC.
Main Methods:
- AIM2 expression was analyzed in OSCC samples using TCGA/GEO databases and RT-PCR.
- Functional assays (colony-forming, trans-well) assessed AIM2's impact on radioresistance and migration.
- AIM2's effect on PD-L1 expression and its regulation by STAT1/NF-κB were examined via RT-PCR, Western blot, flow cytometry, and reporter assays.
Main Results:
- AIM2 is upregulated in OSCC and associated with poor prognosis.
- AIM2 knockdown reduced radioresistance, migration, and PD-L1 expression; overexpression enhanced these.
- AIM2 modulates PD-L1 expression through STAT1/NF-κB pathways.
- Higher AIM2 levels correlated with a favorable response to ICI therapy.
Conclusions:
- AIM2 is a key driver of radioresistance, metastasis, and PD-L1 expression in OSCC.
- AIM2 serves as a potential biomarker for predicting ICI efficacy in refractory OSCC.
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