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Updated: Aug 11, 2026
Th17 Inflammation Model of Oropharyngeal Candidiasis in Immunodeficient Mice
Published on: February 18, 2015
Targeting IL-17alpha to promote anti-PD-1 therapy effect by screening the tumor immune microenvironment in a mouse
Shan Wang1,2,1, Xiaorong Yu3,1, Fang Li4
1Department of Oral Pathology, Hospital of Stomatology, the First Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang, China.
Background:
Resistance to PD-1 blocking agents is not uncommon, limiting their wide clinical success. Certain tumor-infiltrating immune cells (e.g., TILs/CTLs) have emerged as biomarkers of response, and absence of such immune cells contributes to resistance.
Objective:
We deconvoluted the dynamic immune microenvironment in a mouse model of oral carcinogenesis for augmenting the resistance to PD-1 blocking agents by combination.
Methods:
Bioinformatics methods and routine biological experiments were adopted such as morphological analysis and ELISA in the 4NQO-treated mice model.
Results:
Our findings revealed that dysplastic tongue tissues from 4NQO-treated mice were characterized by an immunosuppressive tumor microenvironment. Tongue tissues from mice treated with 4NQO for 12 weeks had higher levels of Th2 cells and Tregs compared to tissues taken from control mice or mice treated with 4NQO for 28 weeks; these results suggested a potential therapeutic benefit of anti-PD-1 in the oral cancer. The IL-17 pathway was significantly upregulated during progression from normal mucosa to hyperplasia and tumor formation in mice. Inhibition of IL-17α combined with PD-1 blockade delayed the development of 4NQO-induced precancerous and cancerous lesions and prolonged the survival of 4NQO-treated mice.
Conclusions:
Our data suggested a strong rationale of IL-17α blockade as a potential approach to augment the tumor-eliminating effects of anti-PD-1 therapy.
Insights
Combining IL-17α blockade with PD-1 blockade can overcome resistance to PD-1 therapy in oral cancer. This combination therapy delays tumor development and improves survival in a mouse model, offering a new strategy for oral cancer treatment.
Area of Science:
- Immunology
- Oncology
- Cancer Research
Background:
- Resistance to PD-1 blocking agents is a significant clinical challenge, often linked to an absence of specific tumor-infiltrating immune cells.
- Understanding the tumor microenvironment is crucial for overcoming immunotherapy resistance.
Purpose of the Study:
- To investigate the immune microenvironment in oral carcinogenesis and identify strategies to enhance PD-1 blockade efficacy through combination therapy.
- To explore the role of the IL-17 pathway in oral cancer progression and its potential as a therapeutic target.
Main Methods:
- Utilized a 4NQO-induced mouse model of oral carcinogenesis.
- Employed bioinformatics, morphological analysis, and ELISA to analyze the immune microenvironment.
- Assessed the therapeutic effects of combined IL-17α and PD-1 blockade.
Main Results:
- Dysplastic tongue tissues exhibited an immunosuppressive microenvironment with increased Th2 cells and Tregs.
- The IL-17 pathway was significantly upregulated during oral cancer progression.
- Combined IL-17α inhibition and PD-1 blockade delayed lesion development and prolonged survival in mice.
Conclusions:
- IL-17α blockade is a promising strategy to enhance the efficacy of anti-PD-1 therapy in oral cancer.
- Targeting the IL-17 pathway in combination with PD-1 blockade offers a potential therapeutic approach for oral cancer.
