Early Posttransplant Mobilization of Monocytic Myeloid-derived Suppressor Cell Correlates With Increase in Soluble Immunosuppressive Factors and Predicts Cancer in Kidney Recipients. Issue 12 (December 2020)

• Record Type: Journal Article
• Authors: Utrero-Rico, Alberto; Laguna-Goya, Rocio; Cano-Romero, Francisco; Chivite-Lacaba, Marta; Gonzalez-Cuadrado, Cecilia; Rodríguez-Sánchez, Elena; Ruiz-Hurtado, Gema; Serrano, Antonio; Fernández-Ruiz, Mario; Justo, Iago; González, Esther; Andrés, Amado; Paz-Artal, Estela
• Is Part Of: Transplantation. Volume 104:Issue 12(2020)
• Publication Date: 2020-12
• Subjects: Transplantation of organs, tissues, etc -- Periodicals; Transplantation immunology -- Periodicals; 617.95
• DOI: 10.1097/TP.0000000000003179
• Languages: English
• ISSNs: 0041-1337

Abstract

Abstract : 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. CD11b + CD33 + CD14 + CD15 - HLA-DR –/low (monocytic MDSC [M-MDSC]) and CD11b + CD33 + CD14 + CD15 – HLA-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. Abstract : Supplemental Digital Content is available in the text.