In the D-first trial, conducted in Japan, 52 patients with newly diagnosed chronic myeloid leukaemia (CML) received the tyrosine kinase inhibitor dasatinib and were monitored for at least 36 months. The cumulative deep molecular response (DMR) rate at 36 months was 65%, and the 3-year overall survival was 96%. T cell counts were stable in these patients over time, but the number of regulatory T (Treg) cells decreased. Moreover, the number and degree of differentiation of natural killer (NK) cells, and the number of cytotoxic T cells were inversely correlated with that of Treg cells. The DMR rate at 12 months was <5.7% in patients with low Treg cell counts, which was significantly more favourable than that of the other patients (odds ratio 4.07). These results suggest that dasatinib inhibits Treg cell proliferation and function, leading to reduced suppression of the immune response, in particular, that dependent on NK cells.
References
Najima, Y. et al. Regulatory T cell inhibition by dasatinib is associated with natural killer cell differentiation and a favorable molecular response — the final results of the D-first study. Leuk. Res. https://doi.org/10.1016/j.leukres.2018.01.010 (2018)
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Romero, D. Dasatinib regulates immune cell function. Nat Rev Clin Oncol 15, 200 (2018). https://doi.org/10.1038/nrclinonc.2018.25
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DOI: https://doi.org/10.1038/nrclinonc.2018.25
