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

Yuho Najima, Chikashi Yoshida, Noriyoshi Iriyama, Shin Fujisawa, Hisashi Wakita, Shigeru Chiba, Shinichiro Okamoto, Kimihiro Kawakami, Naoki Takezako, Takashi Kumagai, Kazuma Ohyashiki, Jun Taguchi, Shingo Yano, Tadahiko Igarashi, Yasuji Kouzai, Satoshi Morita, Junichi Sakamoto, Hisashi Sakamaki, Koiti Inokuchi

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10 Citations (Scopus)

Abstract

We evaluated the effects of regulatory T cell (Treg) inhibition during dasatinib treatment on the anticancer immune response, particularly on natural killer (NK) cells and cytotoxic T lymphocytes (CTLs). Fifty-two newly diagnosed Japanese patients with chronic myeloid leukemia (CML) in the chronic phase were enrolled in the D-first study; all received 100 mg of dasatinib once daily and were followed for at least 36 months. The cumulative deep molecular response (DMR, MR4) rate was 65% by 36 months; the 3-year overall survival was 96%. CD4+ T cell counts were stable, whereas the proportion of CD4+CD25+CD127low (Treg) cells decreased in a time-dependent manner. The DMR rate by18 months was significantly better in low Treg patients (<5.7% at 12 months) compared to the remaining patients (odds ratio 4.07). NK cell and CTL counts at several time points were inversely correlated with Treg counts. Furthermore, the degree of NK cell differentiation (CD3CD57+/CD3CD56+) was closely and inversely correlated with the proportion of Treg cells throughout the observation period, and showed a gradually increasing trend. In conclusion, our results demonstrate that Treg inhibition by dasatinib contributes to better treatment response through enhancement of the immune system, particularly via NK cell differentiation.

Original languageEnglish
Pages (from-to)66-72
Number of pages7
JournalLeukemia Research
Volume66
DOIs
Publication statusPublished - 2018 Mar

Keywords

  • Chronic myeloid leukemia
  • Dasatinib
  • Natural killer cell
  • Regulatory T cell

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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    Najima, Y., Yoshida, C., Iriyama, N., Fujisawa, S., Wakita, H., Chiba, S., Okamoto, S., Kawakami, K., Takezako, N., Kumagai, T., Ohyashiki, K., Taguchi, J., Yano, S., Igarashi, T., Kouzai, Y., Morita, S., Sakamoto, J., Sakamaki, H., & Inokuchi, K. (2018). 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. Leukemia Research, 66, 66-72. https://doi.org/10.1016/j.leukres.2018.01.010