Dasatinib Significantly Enhances the Level of Th1 Cells While Decreases the Level of Treg Cells in Chronic Myeloid Leukemia Patients, and Th1 Can be a Potential Marker for Evaluating the Therapeutic Efficacy and Prognosis

In this study, we evaluate the T cell subtypes by flow cytometry on the chronic myeloid leukemia (CML) patients of our center who have received the treatment with dasatinib (n=10), nolotinib (n=26) or imatinib (n=44) for more than 3 months. We also analyze and correlate these data with the clinical remission situations and prognosis. Results: 1. For the anti-cancer cellular immunity associated Th1 cells: 80% of the patients in dasatinib group, 12.5% of the patients in nilotinib group, 27.5% of the patients in imatinib group have a Th1 proportion (Th1/CD4+ T) higher than the upper limit of normal. The statistical analysis shows that the Th1 proportion in dasatinib group (30.86±9.75%) is significantly higher than that in nilotinib group (17.37±9.35%, p=0.00) and in imatinib group (20.79±9.01%, p=0.00). 2. As for the CD8+ T cell proportion (CD8+ T/Lymphocyte) dasatinib group does not show the statistical difference compared with the nilotinib group and the imatinib group respectively (p=0.24; p=0.09). 3. As for the Th2 cell proportion (Th2/CD4+ T), dasatinib group does not show the statistical difference compared with nilotinib group and imatinib group (p=0.96; p=0.62). 4. The Treg proportion (Treg/CD4+ T) in dasatinib group (1.31±0.10%) is significantly lower than that in nilotinib group (2.65±0.97%, p=0.00) and in imatinib group (2.99±1.40%, p=0.00). 5. When we analyzes all the CML patients with a TKI treatment: (1) In those patients with a Th1 proportion above the upper limit of normal _ 25.8% (n=28), 84.62% of these patients obtain CCyR (complete cytogenetic response), 71.43% of these patients obtain MMR (major molecular response ), and 71.43% of these patients obtain MR4.5; (2) In those patients with a Th1 proportion in the normal range _ 11.8-25.8% (n=45), 90.7% of these patients obtain CCyR, 75.56% of these patients obtain MMR, and 75.56% of these patients obtain MR4.5; (3) In those patients with a Th1 proportion below the lower limit of normal _ 11.8% (n=21), 57.14% of these patients obtain CCyR, 47.62% of these patients obtain MMR, and 47.62% of these patients obtain MR4.5. The patients in the high Th1 level or normal Th1 level groups exhibit deeper remission level, which indicates lower risk of disease progression, higher chance for treatment-free and better prognosis. Conclusion: The data of our center indicates that during the TKI treatment for CML patients, the higher or normal level of Th1 may become a potential candidate marker to be monitored, so as to predict the better therapeutic efficacy and prognosis besides CCyR, MMR, and MR4.5. Dasatinib can significantly improve the anti-cancer immunity associated markers compared with nilotinib and imatinib, and this may be the mechanism of dasatinib to bring good therapeutic efficacy and prognosis.