Comprehensive analysis of the immune pattern of T cell subsets in chronic myeloid leukemia before and after TKI treatment

Danlin Yao; Jing Lai; Yuhong Lu; Jun Zhong; Xianfeng Zha; Xin Huang; Lian Liu; Xiangbo Zeng; Shaohua Chen; Jianyu Weng; Xin Du; Yangqiu Li; Ling Xu

doi:10.3389/fimmu.2023.1078118

Comprehensive analysis of the immune pattern of T cell subsets in chronic myeloid leukemia before and after TKI treatment

Front Immunol. 2023 Jan 19:14:1078118. doi: 10.3389/fimmu.2023.1078118. eCollection 2023.

Authors

Danlin Yao^{1

2}, Jing Lai³, Yuhong Lu³, Jun Zhong³, Xianfeng Zha⁴, Xin Huang⁵, Lian Liu¹, Xiangbo Zeng¹, Shaohua Chen¹, Jianyu Weng⁵, Xin Du⁵, Yangqiu Li¹, Ling Xu¹

Affiliations

¹ Key Laboratory for Regenerative Medicine of Ministry of Education, Institute of Hematology, School of Medicine, Jinan University, Guangzhou, China.
² Department of Hematology, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, China.
³ Department of Hematology, First Affiliated Hospital, Jinan University, Guangzhou, China.
⁴ Department of Clinical Laboratory, First Affiliated Hospital, Jinan University, Guangzhou, China.
⁵ Department of Hematology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.

Abstract

Background: Immunological phenotypes and differentiation statuses commonly decide the T cell function and anti-tumor ability. However, little is known about these alterations in CML patients.

Method: Here, we investigated the immunologic phenotypes (CD38/CD69/HLA-DR/CD28/CD57/BTLA/TIGIT/PD-1) of T subsets (TN, TCM, TEM, and TEMRA) in peripheral blood (PB) and bone marrow (BM) from de novo CML patients (DN-CML), patients who achieved a molecular response (MR) and those who failed to achieve an MR (TKI-F) after tyrosine kinase inhibitor (TKI) treatment using multicolor flow cytometry.

Results: CD38 or HLA-DR positive PB CD8+TN and TCM cells decreased in the DN-CML patients and this was further decreased in TKI-F patients. Meanwhile, the level of PD-1 elevated in CD8+ TEM and TEMRA cells from PB in all groups. Among BM sample, the level of HLA-DR+CD8+TCM cells significantly decreased in all groups and CD8+TEMRA cells from TKI-F patients exhibited increased level of TIGIT and CD8+ tissue-residual T cells (TRM) from DN-CML patients expressed a higher level of PD-1 and TIGIT. Lastly, we found a significantly decreased proportion of CD86+ dendritic cells (DCs) and an imbalanced CD80/CD86 in the PB and BM of DN-CML patients, which may impair the activation of T cells.

Conclusion: In summary, early differentiated TN and TCM cells from CML patients may remain in an inadequate activation state, particularly for TKI-F patients. And effector T cells (TEM, TEMRA and TRM) may be dysfunctional due to the expression of PD-1 and TIGIT in CML patients. Meanwhile, DCs cells exhibited the impairment of costimulatory molecule expression in DN-CML patients. Those factors may jointly contribute to the immune escape in CML patients.

Keywords: CML; T cell subsets; bone marrow microenvironment; immunological phenotypes; tyrosine kinase inhibitor.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Humans
Leukemia, Myelogenous, Chronic, BCR-ABL Positive*
Leukemia, Myeloid*
Programmed Cell Death 1 Receptor / metabolism
T-Lymphocyte Subsets
Tyrosine Kinase Inhibitors / therapeutic use

Substances

Programmed Cell Death 1 Receptor
Tyrosine Kinase Inhibitors

Grants and funding

This work was supported by the [National Natural Science Foundation of China] under Grant [Nos. 82000108, 82070152, 91642111, 82293630, 82293632, 81890991], [China postdoctoral science foundation] under Grant [No. 2018M640884], [Guangdong Province Science and Technology Project] under Grant [2020A1515110310], [Guangzhou Science and Technology Project] under Grant [201803040017], and [Key Laboratory for Regenerative Medicine of Ministry of Education Project] under Grant[ZSYXM202001].