Early Posttransplant Mobilization of Monocytic Myeloid-derived Suppressor Cell Correlates With Increase in Soluble Immunosuppressive Factors and Predicts Cancer in Kidney Recipients.
Adolescent
Adult
Aged
Aged, 80 and over
Case-Control Studies
Cell Proliferation
Cells, Cultured
Coculture Techniques
Female
Humans
Immunocompromised Host
Immunosuppressive Agents
/ adverse effects
Kidney Transplantation
/ adverse effects
Lymphocyte Activation
/ drug effects
Lymphocytes
/ drug effects
Male
Middle Aged
Myeloid-Derived Suppressor Cells
/ drug effects
Neoplasms
/ blood
Phenotype
Prospective Studies
Risk Assessment
Risk Factors
Time Factors
Treatment Outcome
Tumor Escape
Tumor Microenvironment
Young Adult
Journal
Transplantation
ISSN: 1534-6080
Titre abrégé: Transplantation
Pays: United States
ID NLM: 0132144
Informations de publication
Date de publication:
12 2020
12 2020
Historique:
pubmed:
19
2
2020
medline:
9
2
2021
entrez:
19
2
2020
Statut:
ppublish
Résumé
Myeloid-derived suppressor cells (MDSCs) increase in patients with cancer and are associated with poor prognosis; however, their role in transplantation is not yet understood. Here we aimed to study the MDSC effects on the evolution of kidney transplant recipients (KTRs). A cohort of 229 KTRs was prospectively analyzed. Two myeloid cells subsets. CD11bCD33CD14CD15HLA-DR (monocytic MDSC [M-MDSC]) and CD11bCD33CD14CD15HLA-DR (monocytes), were defined by flow cytometry. The suppressive capacity of myeloid cells was tested in cocultures with autologous lymphocytes. Suppressive soluble factors, cytokines, anti-HLA antibodies, and total antioxidant capacity were quantified in plasma. Pretransplant, M-MDSC, and monocytes were similar in KTRs and healthy volunteers. M-MDSCs increased immediately posttransplantation and suppressed CD4 and CD8 T cells proliferation. M-MDSCs remained high for 1 y posttransplantation. Higher M-MDSC counts at day 14 posttransplant were observed in patients who subsequently developed cancer, and KTRs with higher M-MDSC at day 14 had significantly lower malignancy-free survival. Day 14 M-MDSC >179.2 per microliter conferred 6.98 times (95% confidence interval, 1.28-37.69) more risk to develop cancer, independently from age, gender, and immunosuppression. Early posttransplant M-MDSCs were lower in patients with enhanced alloimmune response as represented by anti-HLA sensitization. M-MDSC counts correlated with higher circulatory suppressive factors arginase-1 and interleukin-10, and lower total antioxidant capacity. Early posttransplant mobilization of M-MDSCs predicts cancer and adds risk as an independent factor. M-MDSC may favor an immunosuppressive environment that promotes tumoral development.
Sections du résumé
BACKGROUND
Myeloid-derived suppressor cells (MDSCs) increase in patients with cancer and are associated with poor prognosis; however, their role in transplantation is not yet understood. Here we aimed to study the MDSC effects on the evolution of kidney transplant recipients (KTRs).
METHODS
A cohort of 229 KTRs was prospectively analyzed. Two myeloid cells subsets. CD11bCD33CD14CD15HLA-DR (monocytic MDSC [M-MDSC]) and CD11bCD33CD14CD15HLA-DR (monocytes), were defined by flow cytometry. The suppressive capacity of myeloid cells was tested in cocultures with autologous lymphocytes. Suppressive soluble factors, cytokines, anti-HLA antibodies, and total antioxidant capacity were quantified in plasma.
RESULTS
Pretransplant, M-MDSC, and monocytes were similar in KTRs and healthy volunteers. M-MDSCs increased immediately posttransplantation and suppressed CD4 and CD8 T cells proliferation. M-MDSCs remained high for 1 y posttransplantation. Higher M-MDSC counts at day 14 posttransplant were observed in patients who subsequently developed cancer, and KTRs with higher M-MDSC at day 14 had significantly lower malignancy-free survival. Day 14 M-MDSC >179.2 per microliter conferred 6.98 times (95% confidence interval, 1.28-37.69) more risk to develop cancer, independently from age, gender, and immunosuppression. Early posttransplant M-MDSCs were lower in patients with enhanced alloimmune response as represented by anti-HLA sensitization. M-MDSC counts correlated with higher circulatory suppressive factors arginase-1 and interleukin-10, and lower total antioxidant capacity.
CONCLUSIONS
Early posttransplant mobilization of M-MDSCs predicts cancer and adds risk as an independent factor. M-MDSC may favor an immunosuppressive environment that promotes tumoral development.
Identifiants
pubmed: 32068661
doi: 10.1097/TP.0000000000003179
pii: 00007890-202012000-00026
doi:
Substances chimiques
Immunosuppressive Agents
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2599-2608Références
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