Deficiency of Kif15 gene inhibits tumor growth due to host CD8+T lymphocytes increase

Abstract

Kif15, also name kinesin-12, is a microtubule (MT) associate protein, which functions as a regulator of MT-dependent transport or spindle organization. Previous studies reported Kif15 increases in many tumors, however the effect of host Kif15 gene lack on tumor growth is not investigated. In this study, CRISPR/Cas9 mediated Kif15 gene knockout (Kif15^-/-) mice were established and HE (Hematoxylin-Eosin) assay revealed no significant differences of morphology in most adult tissues (heart, liver, lung, kidney, and brain) except a retarded development of spleen in adult Kif15^-/- mice. RNA sequence analysis of adult spleen tissues of Kif15^-/- and Kif15^+/+ mice was performed, and the results revealed that a total of 438 mRNAs were significantly differentially expressed in Kif15 knockout spleen, showing the top biological process was immune system process. FCM (Flow Cytometry) assay showed the percentage of CD8⁺ T lymphocytes notably increased in spleens of 9 w and 12 w old Kif15^-/- mice. The CD8⁺ T lymphocytes are cytotoxic effector cells fighting against tumor. We thus detected the tumor growth in Kif15^-/- mice using the melanoma cells inoculated subcutaneously. The tumor size significantly reduced in Kif15^-/- mice. We finally detected whether Kif15 dysfunction affects the phagocytic function of macrophages on tumor cells, and the result showed Kif15 inhibitor treated macrophages significantly promoted the phagocytosis in vitro. In summary, this study revealed that the tumor-bearing mice of Kif15 gene deficiency notably inhibited tumor growth due to innate immune activation, which was the first report of the relation of Kif15 on the immunoreactivity.