Imatinib Mesylate Exerted Antitumor Effect by Promoting Infiltration of Effector T Cells in Tumor.

ABSTRACT

Imatinib mesylate is a potent tyrosine kinase inhibitor that may induce immunological effects, such as inhibition of immune suppressive cells; but, how it modulates the immune system remains to be completely elucidated. In this study, we showed that cell proliferation of CT26 colon cancer and Lewis lung carcinoma (3LL) lung cancer cells was not inhibited by imatinib in vitro, although its administration significantly suppressed the growth of CT26, but not 3LL, subcutaneous tumors, and prolonged survival in CT26 tumor-bearing mice. Further, we examined the expression of immune cell-related molecules in the tumors to elucidate the differences in imatinib-mediated antitumor effects between CT26 and 3LL tumors. The nCounter assay showed that the expression of CD8 and CD8+ T cell-recruiting chemokine genes was significantly elevated in imatinib-treated CT26 tumors than that in control tumors; however, the gene expression remained unchanged in imatinib-treated or control 3LL tumors. Furthermore, frequency of interferon-γ+ (IFN-γ+) CD8+ T cells was increased in imatinib-treated CT26 tumors than control tumors, indicating induction of antitumor immunity by imatinib. The analysis indicates that imatinib promotes infiltration of effector T cells in tumors by upregulating expression of cytokines that recruit CD8+ T cells in the tumor microenvironment, which may lead to a strong antitumor effect.