NDLI: BCL-2 expression promotes immunosuppression in chronic lymphocytic leukemia by enhancing regulatory T cell differentiation and cytotoxic T cell exhaustion

Content Provider	Springer Nature : BioMed Central
Author	Liu, Lu Cheng, Xianfeng Yang, Hui Lian, Senlin Jiang, Yuegen Liang, Jinhua Chen, Xiao Mo, Suo Shi, Yu Zhao, Sishu Li, Jianyong Jiang, Runqiu Yang, Dong-Hua Wu, Yujie
Abstract	Background Chronic lymphocytic leukemia (CLL) results in increased susceptibility to infections. T cell dysfunction is not associated with CLL in all patients; therefore, it is important to identify CLL patients with T cell defects. The role of B-cell lymphoma-2 (BCL-2) in CLL has been explored; however, few studies have examined its role in T cells in CLL patients. Herein, we have investigated the regulatory role of BCL-2 in T cells in the CLL tumor microenvironment. Methods The expression of BCL-2 in T cells was evaluated using flow cytometry. The regulatory roles of BCL-2 were investigated using single-cell RNA sequencing (scRNA-seq) and verified using multi-parameter flow cytometry on CD4 and CD8 T cells. The clinical features of BCL-2 expression in T cells in CLL were also explored. Results We found a significant increase in BCL-2 expression in the T cells of CLL patients (n = 266). Single cell RNA sequencing (scRNA-seq) indicated that BCL-2+CD4+ T cells had the gene signature of increased regulatory T cells (Treg); BCL-2+CD8+ T cells showed the gene signature of exhausted cytotoxic T lymphocytes (CTL); and increased expression of BCL-2 was associated with T cell activation and cellular adhesion. The results from scRNA-seq were verified in peripheral T cells from 70 patients with CLL, wherein BCL-2+CD4+ T cells were enriched with Tregs and had higher expression of interleukin-10 and transforming growth factor-β than BCL-2−CD4+ T cells. BCL-2 expression in CD8+T cells was associated with exhausted cells (PD-1+Tim-3+) and weak expression of granzyme B and perforin. T cell–associated cytokine profiling revealed a negative association between BCL-2+ T cells and T cell activation. Decreased frequencies and recovery functions of BCL-2+T cells were observed in CLL patients in complete remission after treatment with venetoclax. Conclusion BCL-2 expression in the T cells of CLL patients is associated with immunosuppression via promotion of Treg abundance and CTL exhaustion.
Related Links	https://molecular-cancer.biomedcentral.com/counter/pdf/10.1186/s12943-022-01516-w.pdf
Ending Page	19
Page Count	19
Starting Page	1
File Format	HTM / HTML
ISSN	14764598
DOI	10.1186/s12943-022-01516-w
Journal	Molecular Cancer
Issue Number	1
Volume Number	21
Language	English
Publisher	BioMed Central
Publisher Date	2022-02-22
Access Restriction	Open
Subject Keyword	Cancer Research Oncology Chronic lymphocytic leukemia T cells BCL-2 Single-cell RNA sequencing
Content Type	Text
Resource Type	Article
Subject	Oncology Molecular Medicine Cancer Research
Journal Impact Factor	27.7/2023
5-Year Journal Impact Factor	31.3/2023

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