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Human G-MDSCs are neutrophils at distinct maturation stages promoting tumor growth in breast cancer

Mehmeti-Ajradini, Meliha LU ; Bergenfelz, Caroline LU ; Larsson, Anna Maria LU ; Carlsson, Robert LU ; Riesbeck, Kristian LU orcid ; Ahl, Jonas LU ; Janols, Helena LU ; Wullt, Marlene LU ; Bredberg, Anders LU and Kallberg, Eva LU , et al. (2020) In Life Science Alliance 3(11).
Abstract

Myeloid-derived suppressor cells (MDSCs) are known to contribute to immune evasion in cancer. However, the function of the human granulocytic (G)-MDSC subset during tumor progression is largely unknown, and there are no established markers for their identification in human tumor specimens. Using gene expression profiling, mass cytometry, and tumor microarrays, we here demonstrate that human G-MDSCs occur as neutrophils at distinct maturation stages, with a disease-specific profile. G-MDSCs derived from patients with metastatic breast cancer and malignant melanoma display a unique immature neutrophil profile, that is more similar to healthy donor neutrophils than to G-MDSCs from sepsis patients. Finally, we show that primary G-MDSCs from... (More)

Myeloid-derived suppressor cells (MDSCs) are known to contribute to immune evasion in cancer. However, the function of the human granulocytic (G)-MDSC subset during tumor progression is largely unknown, and there are no established markers for their identification in human tumor specimens. Using gene expression profiling, mass cytometry, and tumor microarrays, we here demonstrate that human G-MDSCs occur as neutrophils at distinct maturation stages, with a disease-specific profile. G-MDSCs derived from patients with metastatic breast cancer and malignant melanoma display a unique immature neutrophil profile, that is more similar to healthy donor neutrophils than to G-MDSCs from sepsis patients. Finally, we show that primary G-MDSCs from metastatic breast cancer patients cotransplanted with breast cancer cells, promote tumor growth, and affect vessel formation, leading to myeloid immune cell exclusion. Our findings reveal a role for human G-MDSC in tumor progression and have clinical implications also for targeted immunotherapy.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Life Science Alliance
volume
3
issue
11
article number
e202000893
publisher
Rockefeller University Press
external identifiers
  • pmid:32958605
  • scopus:85091472687
ISSN
2575-1077
DOI
10.26508/LSA.202000893
language
English
LU publication?
yes
id
6330eeca-6e27-4ac5-9026-ef1631ab17db
date added to LUP
2020-10-22 16:02:32
date last changed
2023-09-24 10:53:16
@article{6330eeca-6e27-4ac5-9026-ef1631ab17db,
  abstract     = {{<p>Myeloid-derived suppressor cells (MDSCs) are known to contribute to immune evasion in cancer. However, the function of the human granulocytic (G)-MDSC subset during tumor progression is largely unknown, and there are no established markers for their identification in human tumor specimens. Using gene expression profiling, mass cytometry, and tumor microarrays, we here demonstrate that human G-MDSCs occur as neutrophils at distinct maturation stages, with a disease-specific profile. G-MDSCs derived from patients with metastatic breast cancer and malignant melanoma display a unique immature neutrophil profile, that is more similar to healthy donor neutrophils than to G-MDSCs from sepsis patients. Finally, we show that primary G-MDSCs from metastatic breast cancer patients cotransplanted with breast cancer cells, promote tumor growth, and affect vessel formation, leading to myeloid immune cell exclusion. Our findings reveal a role for human G-MDSC in tumor progression and have clinical implications also for targeted immunotherapy. </p>}},
  author       = {{Mehmeti-Ajradini, Meliha and Bergenfelz, Caroline and Larsson, Anna Maria and Carlsson, Robert and Riesbeck, Kristian and Ahl, Jonas and Janols, Helena and Wullt, Marlene and Bredberg, Anders and Kallberg, Eva and Gunnarsdottir, Frida Bjork and Millrud, Camilla Rydberg and Ryden, Lisa and Paul, Gesine and Loman, Niklas and Adolfsson, Jorgen and Carneiro, Ana and Jirstrom, Karin and Killander, Fredrika and Bexell, Daniel and Leandersson, Karin}},
  issn         = {{2575-1077}},
  language     = {{eng}},
  number       = {{11}},
  publisher    = {{Rockefeller University Press}},
  series       = {{Life Science Alliance}},
  title        = {{Human G-MDSCs are neutrophils at distinct maturation stages promoting tumor growth in breast cancer}},
  url          = {{http://dx.doi.org/10.26508/LSA.202000893}},
  doi          = {{10.26508/LSA.202000893}},
  volume       = {{3}},
  year         = {{2020}},
}