Impact of Tyrosine Kinase Inhibitors on T cell function
Dasatinib and nilotinib are front line Tyrosine Kinase Inhibitors (TKIs) used to treat BCR-ABL+ B cell leukemia. While nilotinib is highly specific in its inhibition of ABL, Dasatinib also targets Src-family kinases that regulate TCR signaling. In spite of differences in their ability to impact TCR signaling, the clinical impact of TKIs on the anti-tumor T cell response is not well understood. We thus analyzed how dasatinib and nilotinib impact T cells and tumor control. Here, we show that dasatinib inhibited T cell proliferation at high doses in-vitro, but neither TKI singifincatly impacts T cell functions or expansion in response to immunization in-vivo. We previously showed that combining nilotinib with PDL1 blockade resulted in significant synergistic efficacy, which was abrogated in the absence of CD4 or CD8 T cells. Here, we showed that leukemic mice treated with nilotinib and PDL1 blockade have better survival than mice treated with dasatinib and PDL1 blockade. Thus, dasatinib may negatively impact protective anti-leukemia T cell responses that prevent leukemia relapse.