Interleukin-7 Enhances the in Vivo Anti-tumor Activity of Tumor-reactive CD8+ T cells with Induction of IFN-gamma in a Murine Breast Cancer Model

Interleukin-7 (IL-7) is a potent anti-apoptotic cytokine that enhances immune effector cell functionsand is essential for lymphocyte survival. While it known to induce differentiation and proliferation in somehaematological malignancies, including certain types of leukaemias and lymphomas, little is known about itsrole in solid tumours, including breast cancer. In the current study, we investigated whether IL-7 could enhancethe in vivo antitumor activity of tumor-reactive CD8+ T cells with induction of IFN-γ in a murine breast cancermodel. Human IL-7 cDNA was constructed into the eukaryotic expression plasmid pcDNA3.1, and then therecombinational pcDNA3.1-IL-7 was intratumorally injected in the TM40D BALB/C mouse graft model. Serumand intracellular IFN-γ levels were measured by ELISA and flow cytometry, respectively. CD8+ T cell-mediatedcytotoxicity was analyzed using the MTT method. Our results showed that IL-7 administration significantlyinhibited tumor growth from day 15 after direct intratumoral injection of pcDNA3.1-IL-7. The anti-tumoreffect correlated with a marked increase in the level of IFN-γ and breast cancer cells-specific CTL cytotoxicity.In vitro cytotoxicity assays showed that IL-7-treatment could augment cytolytic activity of CD8+ T cells fromtumor bearing mice, while anti-IFN-γ blocked the function of CD8+ T cells, suggesting that IFN-γ mediated thecytolytic activity of CD8+ T cells. Furthermore, in vivo neutralization of CD8+ T lymphocytes by CD8 antibodiesreversed the antitumor benefit of IL-7. Thus, we demonstrated that IL-7 exerts anti-tumor activity mainly throughactivating CD8+ T cells and stimulating them to secrete IFN-γ in a murine breast tumor model. Based on theseresults, our study points to a potential novel way to treat breast cancer and may have important implicationsfor clinical immunotherapy.