Re-balance of memory T cell subsets in peripheral blood from patients with CML after TKI treatment

Danlin Yao; Ling Xu; Jiaxiong Tan; Yikai Zhang; Shuai Lu; Mingde Li; Sichun Lu; Lijian Yang; Shaohua Chen; Jie Chen; Jing Lai; Yuhong Lu; Xiuli Wu; Xianfeng Zha; Yangqiu Li

doi:10.18632/oncotarget.20965

Re-balance of memory T cell subsets in peripheral blood from patients with CML after TKI treatment

Oncotarget. 2017 Sep 16;8(47):81852-81859. doi: 10.18632/oncotarget.20965. eCollection 2017 Oct 10.

Authors

Danlin Yao^{1

2}, Ling Xu^{1

2}, Jiaxiong Tan^{1

2}, Yikai Zhang^{1

2}, Shuai Lu¹, Mingde Li^{1

2}, Sichun Lu^{1

2}, Lijian Yang¹, Shaohua Chen¹, Jie Chen², Jing Lai², Yuhong Lu², Xiuli Wu^{1

2}, Xianfeng Zha³, Yangqiu Li^{1

2}

Affiliations

¹ Key Laboratory for Regenerative Medicine of Ministry of Education, Institute of Hematology, Jinan University, School of Medicine, Jinan University, Guangzhou, China.
² Department of Hematology, First Affiliated Hospital, Jinan University, Guangzhou, China.
³ Department of Clinical Laboratory, First Affiliated Hospital, Jinan University, Guangzhou, China.

Abstract

T cell immune surveillance is considered an important host protection process for inhibiting carcinogenesis. The full capacity of T cell immune surveillance is dependent on T cell homeostasis, particularly for central memory T (T_CM) cells and stem cell memory T (T_SCM) cells. In this study, distribution of T cell subsets in peripheral blood from 12 patients with chronic myeloid leukemia (CML) and 12 cases with CML in complete remission (CR) was analyzed using a multicolor flow cytometer, and 16 samples from healthy individuals (HIs) served as control. The proportion of CD8⁺ T_SCM and CD4⁺ and CD8⁺ T_CM cells were lower, while CD4⁺ effector memory T (T_EM) cells and CD4⁺ and CD8⁺ terminal effector T (T_EF) cells were higher in CML patients compared with HIs. Moreover, the proportion of CD8⁺CD28^- T cells, which were found to have the immune suppressive function, increased in the naive T (T_N) cell and T_CM subsets in CML patients compared with HIs. Our study reveals that elimination of leukemia cells by treating with tyrosine kinase inhibitors (TKIs) restores the memory T cell distribution from a skewed pattern in CML patients who are under leukemia burden, indicating that leukemia-specific immune responses mediated by T cells might be induced and maintained in CML patients, however, these responsive T cells might gradually become exhausted due to the continued existence of leukemia cells and their environment; therefore, T cell activation using a different approach remains a key point for enhancing global T cell immunity in CML patients, even for those with CR status.

Keywords: CML; Immune response; Immunity; Immunology and Microbiology Section; TKI; TSCM; memory T cells.