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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1424933
This article is part of the Research Topic Mechanisms and Therapeutic Opportunities of T Cell Impairment in Cancer Immunity and Immunotherapy View all articles

Integrative Single-cell Analysis of Longitudinal t(8;21) AML Reveals Heterogeneous Immune Cell Infiltration and Prognostic Signatures

Provisionally accepted
Xueping Li Xueping Li 1*Jiang-Tao Song Jiang-Tao Song 1Yuting Dai Yuting Dai 2Weina Zhang Weina Zhang 3Bati-tian Zhao Bati-tian Zhao 1Jia-Ying Mao Jia-Ying Mao 1Yan Gao Yan Gao 1Lu Jiang Lu Jiang 2Yang Liang Yang Liang 1
  • 1 Sun Yat-sen University Cancer Center (SYSUCC), Guangzhou, China
  • 2 Shanghai Institute of Hematology, Shanghai, Shanghai Municipality, China
  • 3 Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, Guangdong Province, China

The final, formatted version of the article will be published soon.

    Immunotherapies targeting T cells in solid cancers are revolutionizing clinical treatment. Novel immunotherapies have had extremely limited benefit for acute myeloid leukemia (AML). We characterized the immune microenvironment of t(8;21) AML patients to describe its heterogeneity and determine how immune cell infiltration status influences prognosis. Through multi-omics studies of primary and longitudinal t(8;21) AML samples, we characterized the heterogeneous immune cell infiltration in the tumor microenvironment and their immune checkpoint gene expression. CD8+ T cells were enriched and HAVCR2 and TIGIT were upregulated in the CD34 + CD117 dim %-High group; these features are known to be associated with immune exhaustion.Data integration analysis of single-cell dynamics revealed that a subset of T cells (cluster_2) (highly expressing GZMB, NKG7, PRF1 and GNLY) evolved and expanded markedly in the drug-resistant stage after relapse. External cohort analysis confirmed that the cluster_2 T-cell signature could be utilized to stratify patients by overall survival outcome. In conclusion, we discovered a distinct Tcell signature by scRNA-seq that was correlated with disease progression and drug resistance. Our research provides a novel system for classifying patients based on their immune microenvironment.

    Keywords: Single-cell technology, heterogeneity, T cells, AML, prognosis

    Received: 28 Apr 2024; Accepted: 01 Jul 2024.

    Copyright: © 2024 Li, Song, Dai, Zhang, Zhao, Mao, Gao, Jiang and Liang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Xueping Li, Sun Yat-sen University Cancer Center (SYSUCC), Guangzhou, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.