Leptin/lipopolysaccharide-treated dendritic cell vaccine improved cellular immune responses in an animal model of breast cancer.

Purpose: In dendritic cells (DCs), leptin as an immune-regulating hormone, increases the IL-12 generation whereas it reduces the IL-10 production, thus contributing to TH1 cell differentiation. Using a murine model of breast cancer (BC), we evaluated the impacts of the Leptin and/or lipopolysaccharide (LPS)-treated DC vaccine on various T-cell-related immunological markers.

Materials And Methods: Tumors were established in mice by subcutaneously injecting 7 × 10 4T1 cells into the right flank. Mice received the DC vaccines pretreated with Leptin, LPS, and both Leptin/LPS, on days 12 and 19 following tumor induction. The animals were sacrificed on day 26 and after that the frequency of the splenic cytotoxic T lymphocytes (CTLs) and TH1 cells; interferon gamma (IFN-γ), interleukin 12 (IL-12) and tumor growth factor beta (TGF-β) generation by tumor lysate-stimulated spleen cells, and the mRNA expression of T-bet, FOXP3 and Granzyme B in the tumors were measured with flow cytometry, ELISA and real-time PCR methods, respectively.

Results: Leptin/LPS-treated mDC group was more efficient in blunting tumor growth ( = .0002), increasing survival rate ( = .001), and preventing metastasis in comparison with the untreated tumor-bearing mice (UT-control). In comparison to the UT-control group, treatment with Leptin/LPS-treated mDC also significantly increased the splenic frequencies of CTLs ( < .001) and TH1 cells ( < .01); promoted the production of IFN-γ ( < .0001) and IL-12 ( < .001) by splenocytes; enhanced the T-bet ( < .05) and Granzyme B ( < .001) expression, whereas decreased the TGF-β and FOXP3 expression ( < .05).

Conclusion: Compared to the Leptin-treated mDC and LPS-treated mDC vaccines, the Leptin/LPS-treated mDC vaccine was more effective in inhibiting BC development and boosting immune responses against tumor.