Dasatinib-induced anti-leukemia cellular immunity through a novel subset of CD57 positive helper/cytotoxic CD4 T cells in chronic myelogenous leukemia patients
Dasatinib induces lymphocytosis of large granular lymphocytes (LGLs) in a proportion of patients with chronic myelogenous leukemia (CML), and is associated with better clinical outcomes. LGLs consist of cytotoxic T lymphocytes and natural killer cells; however, the context and phenotypic/functional features of each type of LGL are unknown. To better define features of these LGLs, we investigated lymphocytosis in CML patients treated with dasatinib. D57-positive and CD4-positive type I T-helper (Th) cells (CD57+ Th cells) rarely occur in CML patients without lymphocytosis and in healthy individuals; however, a substantial increase in the proportion of CD57+ Th cells was observed in CML patients treated with dasatinib. In addition, these cells showed appreciable levels of cytocidal activity via cytotoxic degranulation. Analysis of T-cell receptor α and β sequences showed a skewed T-cell repertoire in the CD57+ Th cells. Furthermore, patients with LGLs and CD57+ Th lymphocytosis achieved stronger molecular responses than did those without lymphocytosis. While further studies are warranted, our observations suggest that dasatinib induces the expansion of CD57+ Th-LGLs, which may play a crucial role in the dasatinib-induced response against Philadelphia chromosome-positive leukemia.
KeywordsCD57 expression Chronic myelogenous leukemia Cytotoxic CD4+ T cell Dasatinib Large granular lymphocyte
We are grateful to Ryuji Suzuki and Kazutaka Kitaura from Repertoire Genesis Incorporated, for providing technical support.
NW performed the study, analyzed the results, and wrote the paper; TTa designed the research, analyzed the results, wrote the paper, and directed the research; KT and SS analyzed the results; TTo performed the study; MK, MN, and TH contributed analytical materials; HF discussed and analyzed data, provided experimental concepts and materials, and edited the paper; and NK directed the research.
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Conflict of interest
The authors declare that they have no conflict of interest. A summary of relevant information will be published with the manuscript.
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