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

• Published in: Immunopharmacology and immunotoxicology Vol. 46; no. 1; p. 73
• Main Authors: Basirjafar, Pedram, Zandvakili, Raziyeh, Masoumi, Javad, Zainodini, Nahid, Taghipour, Zahra, Khorramdelazad, Hossein, Yousefi, Soheila, Tavakoli, Tayyebeh, Vatanparast, Mahboobeh, Safdel, Sepehr, Gheitasi, Mahsa, Ayoobi, Fatemeh, Naseri, Bahar, Jafarzadeh, Abdollah
• Format: Journal Article
• Language: English
• Published: England 01.02.2024
• Subjects: Animals; Dendritic Cells; Forkhead Transcription Factors - metabolism; Granzymes - metabolism; Immunity, Cellular; Interferon-gamma - metabolism; Interleukin-12; Leptin - metabolism; Lipopolysaccharides - pharmacology; Mice; Models, Animal; Neoplasms - metabolism; Transforming Growth Factor beta - metabolism; Vaccines - metabolism; Breast cancer; lipopolysaccharides; T cells; dendritic cell vaccine; leptin
• ISSN: 1532-2513
• DOI: 10.1080/08923973.2023.2253989

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. 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. 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). 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.