Neospora caninum Inhibits Lewis Cancer and B16f10 Melanoma Lung Metastasis Development by Activating the Immune Response in Murine Models

Malignant tumors are prevalent with high mortality rates in humans, dogs, and cats. Some microorganisms have been shown to inhibit cancer progression. The objective of this study is to evaluate the inhibitory effects of Neospora caninum, a livestock parasite, on three different tumor models in C57BL/6 mice, including Lewis subcutaneous tumors, Lewis and B16F10 melanoma lung metastasis. The results showed that a sufficient amount of N. caninum tachyzoites can significantly inhibit the development of subcutaneous tumors and lung metastasis (P < 0.001), and induce more than 50% tumor cell death in Lewis subcutaneous tumors. N. caninum treatment can significantly increases the infiltration of macrophages, NK cells, and CD8⁺ T cells (P < 0.0001) in Lewis subcutaneous tumors detected by immunohistochemistry, and the percentage of these immunocytes in the spleen (P < 0.05) of mice bearing B16F10 melanoma metastasis detected by flow cytometry. And with these changes, the mRNA expression levels of IL-12, IFN-γ, IL-2, IL-10, TNF-α and PD-L1 in tumor microenvironment and IL-12, IFN-γ, IL-2 in spleen were also significantly increased (P < 0.05). Altogether, our results indicate that a sufficient amount N. caninum tachyzoites not only inhibits the growth of Lewis subcutaneous tumors, but inhibits the development of Lewis and B16F10 melanomas lung metastatic in mice by activating potent immune responses. N. caninum and its anti-tumor properties may be an effective anti-tumor tool.