Expanded tumor-associated polymorphonuclear myeloid-derived suppressor cells in Waldenstrom macroglobulinemia display immune suppressive activity.

Autor: Bhardwaj V; Division of Hematology and Internal Medicine Mayo Clinic, Rochester, MN, USA., Yang ZZ; Division of Hematology and Internal Medicine Mayo Clinic, Rochester, MN, USA., Jalali S; Division of Hematology and Internal Medicine Mayo Clinic, Rochester, MN, USA., Villasboas JC; Division of Hematology and Internal Medicine Mayo Clinic, Rochester, MN, USA., Mudappathi R; Department of Quantitative Health Sciences and Center for Individualized Medicine, Mayo Clinic Arizona, Scottsdale, AZ, USA.; College of Health Solutions, Arizona State University, Phoenix, AZ, USA., Wang J; Department of Quantitative Health Sciences and Center for Individualized Medicine, Mayo Clinic Arizona, Scottsdale, AZ, USA.; Faculty of Dentistry, The University of Hong Kong, Hong Kong SAR, China., Mukherjee P; Division of Hematology and Internal Medicine Mayo Clinic, Rochester, MN, USA., Paludo J; Division of Hematology and Internal Medicine Mayo Clinic, Rochester, MN, USA., Tang X; Division of Hematology and Internal Medicine Mayo Clinic, Rochester, MN, USA., Kim HJ; Division of Hematology and Internal Medicine Mayo Clinic, Rochester, MN, USA., Krull JE; Division of Hematology and Internal Medicine Mayo Clinic, Rochester, MN, USA., Wenzl K; Division of Hematology and Internal Medicine Mayo Clinic, Rochester, MN, USA., Novak AJ; Division of Hematology and Internal Medicine Mayo Clinic, Rochester, MN, USA., Mondello P; Division of Hematology and Internal Medicine Mayo Clinic, Rochester, MN, USA. mondello.patrizia@mayo.edu., Ansell SM; Division of Hematology and Internal Medicine Mayo Clinic, Rochester, MN, USA. ansell.stephen@mayo.edu.
Jazyk: angličtina
Zdroj: Blood cancer journal [Blood Cancer J] 2024 Dec 18; Vol. 14 (1), pp. 217. Date of Electronic Publication: 2024 Dec 18.
DOI: 10.1038/s41408-024-01173-w
Abstrakt: The role of the bone marrow (BM) microenvironment in regulating the antitumor immune response in Waldenstrom macroglobulinemia (WM) remains poorly understood. Here we transcriptionally and phenotypically profiled non-malignant (CD19 - CD138 - ) BM cells from WM patients with a focus on myeloid derived suppressive cells (MDSCs) to provide a deeper understanding of their role in WM. We found that HLA-DR low CD11b + CD33 + MDSCs were significantly increased in WM patients as compared to normal controls, with an expansion of predominantly polymorphonuclear (PMN)-MDSCs. Single-cell immunogenomic profiling of WM MDSCs identified an immune-suppressive gene signature with upregulated inflammatory pathways associated with interferon and tumor necrosis factor (TNF) signaling. Gene signatures associated with an inflammatory and immune suppressive environment were predominately expressed in PMN-MDSCs. In vitro, WM PMN-MDSCs demonstrated robust T-cell suppression and their viability and expansion was notably enhanced by granulocyte colony stimulating factor (G-CSF) and TNFα. Furthermore, BM malignant B-cells attracted PMN-MDSCs to a greater degree than monocytic MDSCs. Collectively, these data suggest that malignant WM B cells actively recruit PMN-MDSCs which promote an immunosuppressive BM microenvironment through a direct T cell inhibition, while release of G-CSF/TNFα in the microenvironment further promotes PMN-MDSC expansion and in turn immune suppression. Targeting PMN-MDSCs may therefore represent a potential therapeutic strategy in patients with WM.
Competing Interests: Competing interests: The authors declare no competing interests. Ethics approval and consent to participate: All methods were carried out in strict accordance with relevant guidelines and regulations. Written informed consent was obtained from all participants in compliance with the Mayo Clinic Institutional Review Board (IRB) requirements (IRB-118-01). The study adhered to the principles outlined in the Declaration of Helsinki.
(© 2024. The Author(s).)
Databáze: MEDLINE
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