CXCR6 defines therapeutic subtypes of CD4 + cytotoxic T cell lineage for adoptive cell transfer therapy in pediatric B cell acute lymphoblastic leukemia.

Autor: Shi S; Department of Immunology, Binzhou Medical University, Yantai, China., Xing H; Department of Allergy, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong 264000, China., Xu X; Department of Immunology, Binzhou Medical University, Yantai, China., Chai J; Department of Immunology, Binzhou Medical University, Yantai, China., Lu Z; Department of Immunology, Binzhou Medical University, Yantai, China., Wang J; Department of Pediatrics, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong 264000, China. Electronic address: ekwjy2012@163.com., Wang B; Department of Immunology, Binzhou Medical University, Yantai, China. Electronic address: bwang_bzmc@bzmc.edu.cn.
Jazyk: angličtina
Zdroj: International immunopharmacology [Int Immunopharmacol] 2024 May 10; Vol. 132, pp. 111972. Date of Electronic Publication: 2024 Apr 02.
DOI: 10.1016/j.intimp.2024.111972
Abstrakt: The potential of cytotoxic CD4 + T cells and tissue resident memory T cells (Trm) in achieving adult leukemia remission have been highlighted [1,2]. We hypothesized that CXCR6 could serve as a marker for cytotoxic CD4 + Trm cells in the bone marrow (BM) of pediatric B-ALL patients. Flow cytometry (FCM) and published single cell RNA sequencing (scRNA-seq) datasets were employed to characterize CXCR6 + CD4 + T cells in the BM and peripheral blood (PB) of pediatric B-ALL patients and healthy donors. FCM, scRNA-seq and co-culture were utilized to explore the cytotoxicity of CXCR6 + CD4 + T cells in vitro based on in vitro induction of CXCR6 + CD4 + T cells using tumor antigens and peripheral blood mononuclear cells (PBMCs). The ssGSEA based on the cell markers identified according to the in vivo scRNA-seq data, the TARGET-ALL-P2 datasets, and integrated machine learning algorithm were employed to figure out the key cells with prognostic values, followed by simulation of adoptive cell transfer therapy (ACT). Integrated machine learning identified the high-risk cells for disease free survival, and overall survival, while simulation of ACT therapy using CXCR6 + CD4 + T cells indicated that CXCR6 + CD4 + T cells could remodel the bone marrow microenvironments towards anti-tumor. Based on the expression of genes involved in formation of resident memory T cells, CXCR6 is not a marker of resident memory CD4 + T cells but defines therapeutic subtypes of CD4 + cytotoxic T cell lineage for pediatric B-ALL.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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