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Published on: April 22, 2019
Elevated Tumor Cell-Intrinsic STING Expression in Advanced Laryngeal Cancer
Jelena Viculin1, Marina Degoricija2, Katarina Vilović3,4
1Department of Oncology and Radiotherapy, University Hospital of Split, 21000 Split, Croatia.
Abstract:
Laryngeal cancer is the second most common malignancy of the head and neck, worldwide. Immunotherapy targeting checkpoint inhibitors has been approved for the treatment of patients with recurrent or metastatic laryngeal cancer but has a relatively low response rate and outcomes that leave many patients underserved. Targeting the cGAS-STING signaling pathway can potentially improve the activation of immune effector cells, although its role in the development and progression of laryngeal cancer has not yet been investigated in depth. Fifty-nine tumor samples from patients with pathologically confirmed squamous cell carcinoma of the larynx, stage I-IV non-metastatic disease, who were treated at the University Hospital of Split, were immunohistochemically stained for the expression of STING, cGAS, CD8, CD68, and CD163. Elevated tumor cell-intrinsic STING expression was positively associated with stage IV (p = 0.0031), pT3, and pT4 laryngeal cancers (p = 0.0336) as well as with higher histological grades (G2 and G3) (p = 0.0204) and lymph node-positive tumors (p = 0.0371). After adjusting for age, sex, location, and cGAS expression, elevated STING expression was significantly associated with stage IV cancer in a multiple logistic regression model (β = 1.849, SE = ±0.8643, p = 0.0324). Elevated STING expression represents a potentially favorable predictive biomarker for new therapeutic approaches involving STING agonists combined with immunotherapy and DNA-damaging agents (radiotherapy, cisplatin, and PARP inhibitors) in laryngeal cancer.
Insights
Elevated STING expression in laryngeal cancer correlates with advanced stages and poor prognosis. This finding suggests STING as a potential biomarker for novel immunotherapies and DNA-damaging treatments.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- Laryngeal cancer is a common head and neck malignancy with limited treatment options for advanced stages.
- Current immunotherapies show low response rates, necessitating novel therapeutic strategies.
- The cGAS-STING pathway's role in laryngeal cancer progression is largely unexplored.
Purpose of the Study:
- To investigate the expression and prognostic significance of the cGAS-STING pathway in laryngeal squamous cell carcinoma.
- To determine if STING expression is associated with clinicopathological features and patient outcomes.
Main Methods:
- Immunohistochemical analysis of STING, cGAS, CD8, CD68, and CD163 in 59 laryngeal cancer tumor samples.
- Correlation analysis between STING expression and clinicopathological parameters (stage, grade, lymph node status).
- Multiple logistic regression to assess STING's independent association with advanced stage.
Main Results:
- Elevated tumor cell-intrinsic STING expression was significantly associated with advanced stage IV disease (p=0.0031), higher T-stage (pT3/pT4), increased histological grade (G2/G3), and lymph node-positive status (p=0.0371).
- STING expression remained a significant predictor of stage IV cancer after adjusting for other factors (β = 1.849, p=0.0324).
Conclusions:
- Elevated STING expression is a potential predictive biomarker in laryngeal cancer.
- STING pathway activation may offer therapeutic targets for combination strategies with immunotherapy and DNA-damaging agents.
- Further research into STING agonists could improve treatment outcomes for laryngeal cancer patients.
