Effect of Immune Checkpoint Blockade on Myeloid-Derived Suppressor Cell Populations in Patients With Melanoma.
Adult
Aged
Antibodies, Monoclonal, Humanized
/ therapeutic use
Cell Count
Female
Humans
Immune Checkpoint Inhibitors
/ therapeutic use
Ipilimumab
/ therapeutic use
Male
Melanoma
/ drug therapy
Middle Aged
Myeloid-Derived Suppressor Cells
/ immunology
Nivolumab
/ therapeutic use
Prospective Studies
Skin Neoplasms
/ drug therapy
MDSC
granulocytic MDSC
immune checkpoint blockade
melanoma
monocytic MDSC
nivolumab
pembrolizumab
Journal
Frontiers in immunology
ISSN: 1664-3224
Titre abrégé: Front Immunol
Pays: Switzerland
ID NLM: 101560960
Informations de publication
Date de publication:
2021
2021
Historique:
received:
13
07
2021
accepted:
23
09
2021
entrez:
29
10
2021
pubmed:
30
10
2021
medline:
6
1
2022
Statut:
epublish
Résumé
Myeloid-derived suppressor cells (MDSC) are a subset of immature myeloid cells that inhibit anti-tumor immunity and contribute to immune therapy resistance. MDSC populations were measured in melanoma patients receiving immune checkpoint inhibitors (ICI). Patients with melanoma (n=128) provided blood samples at baseline (BL), and before cycles 2 and 3 (BC2, BC3). Peripheral blood mononuclear cells (PBMC) were analyzed for MDSC (CD33 Levels of MDSC as a percentage of PBMC increased during ICI (BL: 9.2 ± 1.0% to BC3: 23.6 ± 1.9%, p<0.0001), and patients who developed progressive disease (PD) had higher baseline MDSC. In patients who had a complete or partial response (CR, PR), total MDSC levels rose dramatically and plateaued (BL: 6.4 ± 1.4%, BC2: 26.2 ± 4.2%, BC3: 27.5 ± 4.4%; p<0.0001), whereas MDSC rose less sharply in PD patients (BL: 11.7 ± 2.1%, BC2: 18.3 ± 3.1%, BC3: 19.0 ± 3.2%; p=0.1952). Subset analysis showed that within the expanding MDSC population, PMN-MDSC and E-MDSC levels decreased, while the proportion of M-MDSC remained constant during ICI. In PD patients, the proportion of PMN-MDSC (as a percentage of total MDSC) decreased (BL: 25.1 ± 4.7%, BC2: 16.1 ± 5.2%, BC3: 8.6 ± 1.8%; p=0.0105), whereas a heretofore under-characterized CD14+/CD15+ double positive MDSC subpopulation increased significantly (BL: 8.7 ± 1.4% to BC3: 26.9 ± 4.9%; p=0.0425). MDSC levels initially increased significantly in responders. PMN-MDSC decreased and CD14+CD15+ MDSC increased significantly in PD patients. Changes in MDSC levels may have prognostic value in ICI.
Identifiants
pubmed: 34712230
doi: 10.3389/fimmu.2021.740890
pmc: PMC8547308
doi:
Substances chimiques
Antibodies, Monoclonal, Humanized
0
Immune Checkpoint Inhibitors
0
Ipilimumab
0
Nivolumab
31YO63LBSN
pembrolizumab
DPT0O3T46P
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
740890Subventions
Organisme : NIDDK NIH HHS
ID : R01 DK084725
Pays : United States
Organisme : NCI NIH HHS
ID : UM1 CA186712
Pays : United States
Organisme : NIAID NIH HHS
ID : T32 AI106704
Pays : United States
Informations de copyright
Copyright © 2021 Sun, Benner, Savardekar, Lapurga, Good, Abood, Nagle, Duggan, Stiff, DiVincenzo, Suarez-Kelly, Campbell, Yu, Wesolowski, Howard, Shah, Kendra and Carson.
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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