RT Journal Article SR Electronic 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 FD BMJ Publishing Group Ltd SP e001223 DO 10.1136/jitc-2020-001223 VO 8 IS 2 A1 Luca Cassetta A1 Kirsten Bruderek A1 Joanna Skrzeczynska-Moncznik A1 Oktawia Osiecka A1 Xiaoying Hu A1 Ida Marie Rundgren A1 Ang Lin A1 Kim Santegoets A1 Utku Horzum A1 Ana Godinho-Santos A1 Gennadiy Zelinskyy A1 Thalia Garcia-Tellez A1 Sunčica Bjelica A1 Bartłomiej Taciak A1 Astrid Olsnes Kittang A1 Benedikt Höing A1 Stephan Lang A1 Michael Dixon A1 Verena Müller A1 Jochen Sven Utikal A1 Derya Karakoç A1 Kerim Bora Yilmaz A1 Emilia Górka A1 Lubomir Bodnar A1 Olympia Evdoxia Anastasiou A1 Christine Bourgeois A1 Robert Badura A1 Monika Kapinska-Mrowiecka A1 Mirjana Gotic A1 Mark ter Laan A1 Esther Kers-Rebel A1 Magdalena Król A1 Juan Francisco Santibañez A1 Michaela Müller-Trutwin A1 Ulf Dittmer A1 Ana Espada de Sousa A1 Güneş Esendağlı A1 Gosse Adema A1 Karin Loré A1 Elisabeth Ersvær A1 Viktor Umansky A1 Jeffrey W Pollard A1 Joanna Cichy A1 Sven Brandau YR 2020 UL http://jitc.bmj.com/content/8/2/e001223.abstract AB 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.