Immunosuppressive capacity of circulating MDSC predicts response to immune checkpoint inhibitors in melanoma patients.
MDSC
cytokines
immune checkpoint inhibitors
immunosuppression
melanoma
Journal
Frontiers in immunology
ISSN: 1664-3224
Titre abrégé: Front Immunol
Pays: Switzerland
ID NLM: 101560960
Informations de publication
Date de publication:
2023
2023
Historique:
received:
10
10
2022
accepted:
27
01
2023
entrez:
2
3
2023
pubmed:
3
3
2023
medline:
4
3
2023
Statut:
epublish
Résumé
Although the treatment of advanced melanoma patients with immune checkpoint inhibitors (ICI) significantly increased the therapeutic efficiency, many patients remain resistant to ICI that could be due to immunosuppression mediated by myeloid-derived suppressor cells (MDSC). These cells are enriched and activated in melanoma patients and could be considered as therapeutic targets. Here we studied dynamic changes in immunosuppressive pattern and activity of circulating MDSC from melanoma patients treated with ICI. MDSC frequency, immunosuppressive markers and function were evaluated in freshly isolated peripheral blood mononuclear cells (PBMC) from 29 melanoma patients receiving ICI. Blood samples were taken prior and during the treatment and analyzed by flow cytometry and bio-plex assay. MDSC frequency was significantly increased before the therapy and through three months of treatment in non-responders as compared to responders. Prior to the ICI therapy, MDSC from non-responders displayed high levels of immunosuppression measured by the inhibition of T cell proliferation assay, whereas MDSC from responding patients failed to inhibit T cells. Patients without visible metastasis were characterized by the absence of MDSC immunosuppressive activity during the ICI treatment. Moreover, non-responders showed significantly higher IL-6 and IL-8 concentrations before therapy and after the first ICI application as compared to responders. Our findings highlight the role of MDSC during melanoma progression and suggest that frequency and immunosuppressive activity of circulating MDSC before and during the ICI treatment of melanoma patients could be used as biomarkers of response to ICI therapy.
Identifiants
pubmed: 36860876
doi: 10.3389/fimmu.2023.1065767
pmc: PMC9968744
doi:
Substances chimiques
Immune Checkpoint Inhibitors
0
Immunosuppressive Agents
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1065767Informations de copyright
Copyright © 2023 Petrova, Groth, Bitsch, Arkhypov, Simon, Hetjens, Müller, Utikal and Umansky.
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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