Immunosuppressive cells in acute myeloid leukemia: mechanisms and therapeutic target

Mengnan Liu; Mengting Yang; Mengting Yang; Yue Qi; Yue Qi; Yuting Ma; Yuting Ma; Qulian Guo; Qulian Guo; Ling Guo; Ling Guo; Chunyan Liu; Chunyan Liu; Wenjun Liu; Wenjun Liu; Lan Xiao; Lan Xiao; You Yang; You Yang

doi:10.3389/fimmu.2025.1627161

Frontiers in Immunology (Jul 2025)

Immunosuppressive cells in acute myeloid leukemia: mechanisms and therapeutic target

Mengnan Liu,
Mengting Yang,
Mengting Yang,
Yue Qi,
Yue Qi,
Yuting Ma,
Yuting Ma,
Qulian Guo,
Qulian Guo,
Ling Guo,
Ling Guo,
Chunyan Liu,
Chunyan Liu,
Wenjun Liu,
Wenjun Liu,
Lan Xiao,
Lan Xiao,
You Yang,
You Yang

Affiliations

Mengnan Liu: Department of Cardiovascular Medicine, Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, China
Mengting Yang: Department of Pediatrics (Children Hematological Oncology), Birth Defects and Childhood Hematological Oncology Laboratory, The Affiliated Hospital of Southwest Medical University, Sichuan Clinical Research Center for Birth Defects, Luzhou, Sichuan, China
Mengting Yang: Department of Pediatrics, Southwest Medical University, Luzhou, Sichuan, China
Yue Qi: Department of Pediatrics (Children Hematological Oncology), Birth Defects and Childhood Hematological Oncology Laboratory, The Affiliated Hospital of Southwest Medical University, Sichuan Clinical Research Center for Birth Defects, Luzhou, Sichuan, China
Yue Qi: Department of Pediatrics, Southwest Medical University, Luzhou, Sichuan, China
Yuting Ma: Department of Pediatrics (Children Hematological Oncology), Birth Defects and Childhood Hematological Oncology Laboratory, The Affiliated Hospital of Southwest Medical University, Sichuan Clinical Research Center for Birth Defects, Luzhou, Sichuan, China
Yuting Ma: Department of Pediatrics, Southwest Medical University, Luzhou, Sichuan, China
Qulian Guo: Department of Pediatrics (Children Hematological Oncology), Birth Defects and Childhood Hematological Oncology Laboratory, The Affiliated Hospital of Southwest Medical University, Sichuan Clinical Research Center for Birth Defects, Luzhou, Sichuan, China
Qulian Guo: Department of Pediatrics, Southwest Medical University, Luzhou, Sichuan, China
Ling Guo: Department of Pediatrics (Children Hematological Oncology), Birth Defects and Childhood Hematological Oncology Laboratory, The Affiliated Hospital of Southwest Medical University, Sichuan Clinical Research Center for Birth Defects, Luzhou, Sichuan, China
Ling Guo: Department of Pediatrics, Southwest Medical University, Luzhou, Sichuan, China
Chunyan Liu: Department of Pediatrics (Children Hematological Oncology), Birth Defects and Childhood Hematological Oncology Laboratory, The Affiliated Hospital of Southwest Medical University, Sichuan Clinical Research Center for Birth Defects, Luzhou, Sichuan, China
Chunyan Liu: Department of Pediatrics, Southwest Medical University, Luzhou, Sichuan, China
Wenjun Liu: Department of Pediatrics (Children Hematological Oncology), Birth Defects and Childhood Hematological Oncology Laboratory, The Affiliated Hospital of Southwest Medical University, Sichuan Clinical Research Center for Birth Defects, Luzhou, Sichuan, China
Wenjun Liu: Department of Pediatrics, Southwest Medical University, Luzhou, Sichuan, China
Lan Xiao: Department of Pediatrics (Children Hematological Oncology), Birth Defects and Childhood Hematological Oncology Laboratory, The Affiliated Hospital of Southwest Medical University, Sichuan Clinical Research Center for Birth Defects, Luzhou, Sichuan, China
Lan Xiao: Department of Pediatrics, Southwest Medical University, Luzhou, Sichuan, China
You Yang: Department of Pediatrics (Children Hematological Oncology), Birth Defects and Childhood Hematological Oncology Laboratory, The Affiliated Hospital of Southwest Medical University, Sichuan Clinical Research Center for Birth Defects, Luzhou, Sichuan, China
You Yang: Department of Pediatrics, Southwest Medical University, Luzhou, Sichuan, China

DOI: https://doi.org/10.3389/fimmu.2025.1627161
Journal volume & issue: Vol. 16

Abstract

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Immunotherapy has emerged as a cornerstone strategy for augmenting therapeutic efficacy in acute myeloid leukemia (AML). The immunosuppressive AML microenvironment, characterized by profound immune dysfunction, critically impairs anti-leukemic immune surveillance. This immunologically hostile niche is principally governed by specialized immunosuppressive cell populations—notably regulatory T cells (Tregs), myeloid-derived suppressor cells (MDSCs), leukemia-associated macrophages (LAMs), and regulatory B cells (Bregs)—which collectively establish an immune-privileged sanctuary for leukemic cells. This review critically examines three fundamental aspects of these immunosuppressive regulators in AML pathogenesis: (1) their recruitment dynamics within the leukemic niche, (2) the molecular mechanisms underlying their immunosuppressive functions, and (3) current and emerging therapeutic approaches designed to neutralize their inhibitory effects. Through this comprehensive analysis, we aim to provide a mechanistic framework for developing more effective immunotherapeutic interventions against AML.

Published in Frontiers in Immunology

ISSN: 1664-3224 (Online)
Publisher: Frontiers Media S.A.
Country of publisher: Switzerland
LCC subjects: Medicine: Internal medicine: Specialties of internal medicine: Immunologic diseases. Allergy
Website: http://journal.frontiersin.org/journal/immunology

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