TY - JOUR T1 - Differential expansion of circulating human MDSC subsets in patients with cancer, infection and inflammation JF - Journal for ImmunoTherapy of Cancer JO - J Immunother Cancer DO - 10.1136/jitc-2020-001223 VL - 8 IS - 2 SP - e001223 AU - Luca Cassetta AU - Kirsten Bruderek AU - Joanna Skrzeczynska-Moncznik AU - Oktawia Osiecka AU - Xiaoying Hu AU - Ida Marie Rundgren AU - Ang Lin AU - Kim Santegoets AU - Utku Horzum AU - Ana Godinho-Santos AU - Gennadiy Zelinskyy AU - Thalia Garcia-Tellez AU - Sunčica Bjelica AU - Bartłomiej Taciak AU - Astrid Olsnes Kittang AU - Benedikt Höing AU - Stephan Lang AU - Michael Dixon AU - Verena Müller AU - Jochen Sven Utikal AU - Derya Karakoç AU - Kerim Bora Yilmaz AU - Emilia Górka AU - Lubomir Bodnar AU - Olympia Evdoxia Anastasiou AU - Christine Bourgeois AU - Robert Badura AU - Monika Kapinska-Mrowiecka AU - Mirjana Gotic AU - Mark ter Laan AU - Esther Kers-Rebel AU - Magdalena Król AU - Juan Francisco Santibañez AU - Michaela Müller-Trutwin AU - Ulf Dittmer AU - Ana Espada de Sousa AU - Güneş Esendağlı AU - Gosse Adema AU - Karin Loré AU - Elisabeth Ersvær AU - Viktor Umansky AU - Jeffrey W Pollard AU - Joanna Cichy AU - Sven Brandau Y1 - 2020/09/01 UR - http://jitc.bmj.com/content/8/2/e001223.abstract N2 - Background Myeloid-derived suppressor cells (MDSC) are a functional myeloid cell subset that includes myeloid cells with immune suppressive properties. The presence of MDSC has been reported in the peripheral blood of patients with several malignant and non-malignant diseases. So far, direct comparison of MDSC across different diseases and Centers is hindered by technical pitfalls and a lack of standardized methodology. To overcome this issue, we formed a network through the COST Action Mye-EUNITER (www.mye-euniter.eu) with the goal to standardize and facilitate the comparative analysis of human circulating MDSC in cancer, inflammation and infection. In this manuscript, we present the results of the multicenter study Mye-EUNITER MDSC Monitoring Initiative, that involved 13 laboratories and compared circulating MDSC subsets across multiple diseases, using a common protocol for the isolation, identification and characterization of these cells.Methods We developed, tested, executed and optimized a standard operating procedure for the isolation and immunophenotyping of MDSC using blood from healthy donors. We applied this procedure to the blood of almost 400 patients and controls with different solid tumors and non-malignant diseases. The latter included viral infections such as HIV and hepatitis B virus, but also psoriasis and cardiovascular disorders.Results We observed that the frequency of MDSC in healthy donors varied substantially between centers and was influenced by technical aspects such as the anticoagulant and separation method used. Expansion of polymorphonuclear (PMN)-MDSC exceeded the expansion of monocytic MDSC (M-MDSC) in five out of six solid tumors. PMN-MDSC expansion was more pronounced in cancer compared with infection and inflammation. Programmed death-ligand 1 was primarily expressed in M-MDSC and e-MDSC and was not upregulated as a consequence of disease. LOX-1 expression was confined to PMN-MDSC.Conclusions This study provides improved technical protocols and workflows for the multi-center analysis of circulating human MDSC subsets. Application of these workflows revealed a predominant expansion of PMN-MDSC in solid tumors that exceeds expansion in chronic infection and inflammation. ER -