Vaccination with celecoxib-treated dendritic cells improved cellular immune responses in an animal breast cancer model.

PURPOSE: Prostaglandin E2 (PGE2), a product of cyclooxygenase (COX) pathway of arachidonic acid, exerts inhibitory impacts on dendritic cell (DC) activity to repress anti-tumor immune responses. Therefore, targeting COX during DC vaccine generation may enhance DC-mediated antitumor responses. We aimed to investigate the impacts of DC vaccine treated with celecoxib (CXB), a selective COX2 inhibitor, on some T cell-related parameters.

MATERIALS AND

METHODS

Breast cancer (BC) was induced in BALB/c mice, and then they received DC vaccine treated with lipopolysaccharide (LPS-mDCs), LPS with a 5 ​μM dose of CXB (LPS/CXB5-mDCs) and LPS with a 10 ​μM dose of CXB (LPS/CXB10-mDCs). The frequency of splenic Th1 and Treg cells and amounts of IFN-γ, IL-12 and TGF-β production by splenocytes, as well as, the expression of Granzyme-B, T-bet and FOXP3 in tumors were determined using flow cytometry, ELISA, and real-time PCR, respectively.

RESULTS

Compared with untreated tumor group (T-control), treatment with LPS/CXB5-mDCs and LPS/CXB10-mDCs decreased tumor growth (P ​= ​0.009 and P ​< ​0.0001), escalated survival rate (P ​= ​0.002), increased the frequency of splenic Th1 cells (P ​= ​0.0872, and P ​= ​0.0155), increased the IFN-γ (P ​= ​0.0003 and P ​= ​0.0061) and IL-12 (P ​= ​0.001 and P ​= ​0.0009) production by splenocytes, upregulated T-bet (P ​= ​0.062 and P ​< ​0.0001) and Granzyme-B (P ​= ​0.0448 and P ​= ​0.4485), whereas decreased the number of Treg cells (P ​= ​0.0014, and P ​= ​0.0219), reduced the amounts of TGF-β production by splenocytes (P ​= ​0.0535 and P ​= ​0.0169), and reduced the expression of FOXP3 (P ​= ​0.0006 and P ​= ​0.0057) in comparison with T-control group.

CONCLUSIONS

Our findings show that LPS/CXB-treated DC vaccine potently modulated antitumor immune responses in a mouse BC model.