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Published on: January 3, 2013
B7-H4 expression indicates poor prognosis of oral squamous cell carcinoma
Lei Wu1, Wei-Wei Deng1, Guang-Tao Yu1
1The State Key Laboratory Breeding Base of Basic Science of Stomatology and Key Laboratory of Oral Biomedicine, Ministry of Education, Wuhan University, Wuhan, People's Republic of China.
Abstract:
Checkpoint blockade therapy utilizing monoclonal antibodies to reactivate T cells and recover their antitumor activity makes an epoch in cancer immunotherapy. The role of B7-H4, a novel negative immune checkpoint, in oral squamous cell carcinoma (OSCC) has still not been elucidated. In this study, tissue samples from human OSCC, which contains 165 primary OSCC, 48 oral epithelial dysplasia and 43 normal oral mucosa specimens, and Tgfbr1/Pten 2cKO mice OSCC model were stained with B7-H4 antibody to analyze the correlations between B7-H4 expression and clinicopathological characteristics. Kaplan-Meier analysis was used to compare the survival of patients with high B7-H4 expression and patients with low B7-H4 expression. We found B7-H4 is highly expressed in human OSCC tissue, and the B7-H4 expression level was associated with the clinicopathological parameters containing pathological grade and lymph node status. Moreover, we confirmed that B7-H4 was overexpressed in Tgfbr1/Pten 2cKO mice OSCC model. Our data also indicated that patients with high B7-H4 expression had poor overall survival compared with those with low B7-H4 expression. Furthermore, this study demonstrated that B7-H4 was positively associated with PD-L1, CD11b, CD33, PI3Kα p110, and p-S6 (S235/236). Taken together, these findings suggest B7-H4 is a potential target in the treatment of OSCC.
Insights
B7-H4, a novel immune checkpoint, is highly expressed in oral squamous cell carcinoma (OSCC). High B7-H4 expression correlates with poor survival and is a potential therapeutic target for OSCC treatment.
Area of Science:
- Immunology
- Oncology
- Cancer Research
Background:
- Checkpoint blockade therapy has revolutionized cancer immunotherapy by reactivating T cells.
- The role of the novel immune checkpoint B7-H4 in oral squamous cell carcinoma (OSCC) remains unclear.
Purpose of the Study:
- To investigate the expression of B7-H4 in OSCC.
- To analyze the correlation between B7-H4 expression and clinicopathological characteristics and patient survival.
- To explore potential therapeutic implications of B7-H4 in OSCC.
Main Methods:
- Immunohistochemical staining of B7-H4 in human OSCC tissues, oral epithelial dysplasia, and normal oral mucosa.
- Analysis of B7-H4 expression in a Tgfbr1/Pten 2cKO mice OSCC model.
- Kaplan-Meier survival analysis.
- Correlation analysis with clinicopathological parameters and other molecular markers (PD-L1, CD11b, CD33, PI3Kα p110, p-S6).
Main Results:
- B7-H4 was significantly overexpressed in human OSCC tissues compared to normal mucosa and dysplasia.
- High B7-H4 expression was associated with advanced pathological grade and lymph node metastasis.
- Overexpression of B7-H4 was confirmed in the mouse OSCC model.
- Patients with high B7-H4 expression exhibited significantly poorer overall survival.
- B7-H4 expression positively correlated with PD-L1, CD11b, CD33, PI3Kα p110, and p-S6.
Conclusions:
- B7-H4 is upregulated in OSCC and linked to aggressive clinicopathological features and poor prognosis.
- B7-H4 represents a potential predictive biomarker and therapeutic target for oral squamous cell carcinoma.
