Deciphering neutrophil dynamics in the focal lesion tumor microenvironment to overcome immunosuppression in multiple myeloma

Understanding the roles of myeloid cells in the tumor microenvironment (TME) has emerged as a promising strategy to identify novel targets to counteract the immunosuppressive barriers protecting multiple myeloma (MM). Neutrophils are a new cancer research focus due to their potential to reduce the e...

Full description

Saved in:
Bibliographic Details
Published in:Blood Vol. 146; no. 20; p. 2392
Main Authors: Rivera, Joshua, Yan, Qi, Daneshmandi, Saeed, Lannes, Romain, Katsuta, Eriko, Choi, JeeEun, Singh, Prashant, Belal, Ahmed, Alberico, Ronald, Lund, Ian, Schaefer, Megan, Hassan, Hamza, Parker, Sarah, Anderson, Kenneth C, Munshi, Nikhil C, Samur, Mehmet, McCarthy, Philip L, Hillengass, Jens, Mohammadpour, Hemn
Format: Journal Article
Language:English
Published: United States 13.11.2025
Subjects:
Animals
Female
Humans
Immune Tolerance
Male
Mice
Multiple Myeloma - genetics
Multiple Myeloma - immunology
Multiple Myeloma - pathology
Neutrophils - immunology
Neutrophils - pathology
Receptors, Interleukin-8B
Tumor Microenvironment - immunology
ISSN:1528-0020, 1528-0020
Online Access:Get more information
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Understanding the roles of myeloid cells in the tumor microenvironment (TME) has emerged as a promising strategy to identify novel targets to counteract the immunosuppressive barriers protecting multiple myeloma (MM). Neutrophils are a new cancer research focus due to their potential to reduce the efficacy of immune-based therapies. This study aimed to deepen understanding of neutrophil function in MM by analyzing freshly isolated myeloid cells from paired focal lesions (FLs) and bone marrow using single-cell RNA sequencing, immunofluorescence imaging, and functional assays. We describe 3 distinct CXCR2+ mature neutrophil subsets: TREM1+CD10+, RETN+LCN2+, and TNFAIP3+CXCL8+, each exhibiting unique phenotypes within the TME. Notably, the TREM1+CD10+ subset was highly prevalent, particularly in FLs, demonstrating potent immunosuppressive effects on T cells. This subset's gene signature was correlated with shorter overall survival (OS) in a large data set of patients with MM, underscoring its clinical significance. Targeted inhibition of neutrophil activity through CXCR2 blockade, alone or combined with standard anti-MM therapies, significantly reduced tumor burden, improving OS in preclinical MM models. These insights into neutrophil-mediated immunosuppression in MM provide valuable knowledge regarding mechanisms driving immune evasion, and reveal new therapeutic approaches to enhance the efficacy of MM treatment.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:1528-0020
1528-0020
DOI:10.1182/blood.2025028963