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

Abstract

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 × 10⁵ 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 (p = .0002), increasing survival rate (p = .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 (p < .001) and TH1 cells (p < .01); promoted the production of IFN-γ (p < .0001) and IL-12 (p < .001) by splenocytes; enhanced the T-bet (p < .05) and Granzyme B (p < .001) expression, whereas decreased the TGF-β and FOXP3 expression (p < .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.

Keywords:

• Breast cancer
• dendritic cell vaccine
• leptin
• lipopolysaccharides
• T cells

Author contributions

Abdollah Jafarzadeh contributed to the study conception and design. Data collection and analyses were performed by Pedram Basirjafar, Raziyeh Zandvakili, Javad Masoumi, Nahid Zainodini, Zahra Taghipour, Hossein Khorramdelazad, Soheila Yousefi, Tayyebeh Tavakoli, Mahboobeh Vatanparast, Bahar Naseri, Sepehr Safdel, Mahsa Gheitasi, and Fatemeh Ayoobi. The first draft of the manuscript was written by Pedram Basirjafar, Raziyeh Zandvakili, and Javad Masoumi. Abdollah Jafarzadeh supervised the project and revised the manuscript.

Disclosure statement

The authors have no conflict of interest.

Data availability statement

Data are available on reasonable request from the authors.

Additional information

Funding

This work was supported by a grant (PN: 98104) from the Rafsanjan University of Medical Sciences, Rafsanjan, Iran.