Alberto Utrero-Rico1, Rocio Laguna-Goya1,2, Francisco Cano-Romero1, Marta Chivite-Lacaba1, Cecilia Gonzalez-Cuadrado1, Elena Rodríguez-Sánchez3, Gema Ruiz-Hurtado3,4, Antonio Serrano1,2, Mario Fernández-Ruiz1,5, Iago Justo6, Esther González7, Amado Andrés7, Estela Paz-Artal1,2,8. 1. Immunodeficiencies and Transplant Immunology Group, Instituto de Investigación Sanitaria Hospital Universitario 12 de Octubre (imas 12), Madrid, Spain. 2. Department of Immunology, Hospital Universitario 12 de Octubre, Madrid, Spain. 3. Cardiorenal Translational Laboratory, imas12, Madrid, Spain. 4. CIBER-CV, Hospital Universitario 12 de Octubre, Madrid, Spain. 5. Unit of Infectious Diseases, Hospital Universitario 12 de Octubre, Madrid, Spain. 6. Department of Surgery and Abdominal Organs Transplantation, Hospital Universitario 12 de Octubre, Madrid, Spain. 7. Department of Nephrology, Hospital Universitario 12 de Octubre, Madrid, Spain. 8. Department of Immunology, Oftalmology and ENT, Universidad Complutense de Madrid, Madrid, Spain.
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. 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.
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.
Authors: Andreas Schroeter; Maximilian J Roesel; Tomohisa Matsunaga; Yao Xiao; Hao Zhou; Stefan G Tullius Journal: Front Immunol Date: 2022-07-06 Impact factor: 8.786
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Authors: Elena Rodríguez-Sánchez; José Alberto Navarro-García; Jennifer Aceves-Ripoll; Judith Abarca-Zabalía; Andrea Susmozas-Sánchez; Teresa Bada-Bosch; Eduardo Hernández; Evangelina Mérida-Herrero; Amado Andrés; Manuel Praga; Mario Fernández-Ruiz; José María Aguado; Julián Segura; Luis Miguel Ruilope; Gema Ruiz-Hurtado Journal: Biomolecules Date: 2020-03-26