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Bone Marrow Neutrophils of Multiple Myeloma Patients Exhibit Myeloid-Derived Suppressor Cell Activity

Petersson, Julia LU ; Askman, Sandra LU ; Pettersson, Åsa LU ; Wichert, Stina LU orcid ; Hellmark, Thomas LU orcid ; Johansson, Åsa LU and Hansson, Markus LU orcid (2021) In Journal of Immunology Research 2021. p.1-10
Abstract
Activated normal density granulocytes (NDGs) can suppress T-cell responses in a similar way as myeloid-derived suppressor cells (MDSCs). In this study, we tested the hypothesis that NDGs from blood and bone marrow of multiple myeloma (MM) patients have the ability to suppress T-cells, as MDSC. MM is an incurable plasma cell malignancy of the bone marrow. Like most malignancies, myeloma cells alter its microenvironment to promote tumor growth, including inhibition of the immune system. We found that MM NDG from the bone marrow suppressed proliferation of T-cells, in contrast to healthy donors. The inhibitory effect could not be explained by changed levels of mature or immature NDG in the bone marrow. Moreover, NDG isolated from the blood of... (More)
Activated normal density granulocytes (NDGs) can suppress T-cell responses in a similar way as myeloid-derived suppressor cells (MDSCs). In this study, we tested the hypothesis that NDGs from blood and bone marrow of multiple myeloma (MM) patients have the ability to suppress T-cells, as MDSC. MM is an incurable plasma cell malignancy of the bone marrow. Like most malignancies, myeloma cells alter its microenvironment to promote tumor growth, including inhibition of the immune system. We found that MM NDG from the bone marrow suppressed proliferation of T-cells, in contrast to healthy donors. The inhibitory effect could not be explained by changed levels of mature or immature NDG in the bone marrow. Moreover, NDG isolated from the blood of both myeloma patients and healthy individuals could inhibit T-cell proliferation and IFN-γ production. On the contrary to previous studies, blood NDGs did not have to be preactivated to mediate suppressive effects. Instead, they became activated during coculture, indicating that contact with activated T-cells is important for their ability to regulate T-cells. The inhibitory effect was dependent on the production of reactive oxygen species and could be reverted by the addition of its inhibitor, catalase. Our findings suggest that blood NDGs from MM patients are suppressive, but no more than NDGs from healthy donors. However, only bone marrow NDG from MM patients exhibited MDSC function. This MDSC-like suppression mediated by bone marrow NDG could be important for the growth of malignant plasma cells in MM patients. (Less)
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Immunology Research
volume
2021
article number
6344344
pages
1 - 10
publisher
Hindawi Limited
external identifiers
  • pmid:34414242
  • scopus:85113732583
ISSN
2314-7156
DOI
10.1155/2021/6344344
language
English
LU publication?
yes
id
eeff207d-6a93-41b9-bdad-8586289142e2
date added to LUP
2021-08-26 13:34:08
date last changed
2024-10-20 04:45:00
@article{eeff207d-6a93-41b9-bdad-8586289142e2,
  abstract     = {{Activated normal density granulocytes (NDGs) can suppress T-cell responses in a similar way as myeloid-derived suppressor cells (MDSCs). In this study, we tested the hypothesis that NDGs from blood and bone marrow of multiple myeloma (MM) patients have the ability to suppress T-cells, as MDSC. MM is an incurable plasma cell malignancy of the bone marrow. Like most malignancies, myeloma cells alter its microenvironment to promote tumor growth, including inhibition of the immune system. We found that MM NDG from the bone marrow suppressed proliferation of T-cells, in contrast to healthy donors. The inhibitory effect could not be explained by changed levels of mature or immature NDG in the bone marrow. Moreover, NDG isolated from the blood of both myeloma patients and healthy individuals could inhibit T-cell proliferation and IFN-γ production. On the contrary to previous studies, blood NDGs did not have to be preactivated to mediate suppressive effects. Instead, they became activated during coculture, indicating that contact with activated T-cells is important for their ability to regulate T-cells. The inhibitory effect was dependent on the production of reactive oxygen species and could be reverted by the addition of its inhibitor, catalase. Our findings suggest that blood NDGs from MM patients are suppressive, but no more than NDGs from healthy donors. However, only bone marrow NDG from MM patients exhibited MDSC function. This MDSC-like suppression mediated by bone marrow NDG could be important for the growth of malignant plasma cells in MM patients.}},
  author       = {{Petersson, Julia and Askman, Sandra and Pettersson, Åsa and Wichert, Stina and Hellmark, Thomas and Johansson, Åsa and Hansson, Markus}},
  issn         = {{2314-7156}},
  language     = {{eng}},
  pages        = {{1--10}},
  publisher    = {{Hindawi Limited}},
  series       = {{Journal of Immunology Research}},
  title        = {{Bone Marrow Neutrophils of Multiple Myeloma Patients Exhibit Myeloid-Derived Suppressor Cell Activity}},
  url          = {{http://dx.doi.org/10.1155/2021/6344344}},
  doi          = {{10.1155/2021/6344344}},
  volume       = {{2021}},
  year         = {{2021}},
}