Highly suppressive functional CCR7 ^low Treg subset cells may correlate with poor prognosis of B-ALL.

Authors

Sui Songnan, Jiamian Zheng, Jing Lai, Yupei Zhang, Xu Jiang, Ling Xu, Liye Zhong, Jie Chen, Jie Wu, Xun Zhu, Yangqiu Li, Guocai Wu, Zhanghui Chen

Published in

Hematology (Amsterdam, Netherlands). Volume 31. Issue 1. Pages 2702683. Dec 31, 2026. Epub Jul 28, 2026.

Abstract

Regulatory T cells (Tregs) may influence prognosis in leukemia. This study aimed to explore the effects and mechanisms of Treg subclusters on the prognosis in B-cell acute lymphoblastic leukemia (B-ALL) using single-cell RNA sequencing (scRNA-Seq).
scRNA-seq was performed on sorted T cells from adults with newly diagnosed (Dix) B-ALL and healthy donors (HD) to establish the training cohort. Treg phenotypes, functions, and prognostic relevance were evaluated. A scRNA-seq dataset from the GEO database, including Dix and relapsed B-ALL, served as the validation cohort. Key findings were confirmed by flow cytometry. Transcription factor and cell-cell interaction analyses were conducted to clarify the mechanisms linking Treg subsets to prognosis.
Tregs were divided into CCR7^high and CCR7^low subclusters. The proportion of CCR7^low Tregs was higher in B-ALL than in HD and in Rel than in Dix. Patients with higher CCR7^low Treg signature scores had a poorer prognosis. Compared with CCR7^high Tregs, CCR7^low Tregs exhibited enhanced activation, proliferation, and immunosuppression. Trajectory analysis suggested differentiation from CCR7^high to CCR7^low Tregs. IKZF2 and JUNB showed consistently increased activity and expression in CCR7^low Tregs across cohorts. CCR7^low Tregs showed increased interactions with terminal effector and exhausted CD8⁺ T cells through the LGALS9-P4HB/HAVCR2/CD44 pathway.
An increased proportion of CCR7^low Tregs correlated with poor prognosis in B-ALL, potentially due to enhanced activation, proliferation, and immunosuppression. IKZF2 and JUNB upregulation may promote CCR7^low Treg differentiation and function. Moreover, CCR7^low Tregs may impair CD8⁺ T cell immunity through the LGALS9-P4HB/HAVCR2/CD44 signaling.

PMID:
42517226
Bibliographic data and abstract were imported from PubMed on 28 Jul 2026.

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