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

• Published in: Frontiers in immunology Vol. 14; p. 1078118
• Main Authors: Yao, Danlin, Lai, Jing, Lu, Yuhong, Zhong, Jun, Zha, Xianfeng, Huang, Xin, Liu, Lian, Zeng, Xiangbo, Chen, Shaohua, Weng, Jianyu, Du, Xin, Li, Yangqiu, Xu, Ling
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 19.01.2023
• Subjects: bone marrow microenvironment; CML; Humans; immunological phenotypes; Immunology; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid; Programmed Cell Death 1 Receptor - metabolism; T cell subsets; T-Lymphocyte Subsets; tyrosine kinase inhibitor; Tyrosine Kinase Inhibitors - therapeutic use; CML; tyrosine kinase inhibitor; T cell subsets; bone marrow microenvironment; immunological phenotypes
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2023.1078118

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. 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. 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. 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.