CD73 expression and clinical significance in human metastatic melanoma

// Ines Monteiro 1 , Selena Vigano 2 , Mohamed Faouzi 3 , Isabelle Treilleux 4 , Olivier Michielin 5 , Christine Menetrier-Caux 6, 7 , Christophe Caux 6, 7 , Pedro Romero 2, * and Laurence de Leval 1, * 1 Institute of Pathology, Lausanne University Hospital, Lausanne, Switzerland 2 Department of Oncology, Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland 3 Institute of Social and Preventive Medicine (IUMSP), University Hospital, Lausanne, Switzerland 4 Anatomopathology Department, Centre Leon Berard, Lyon, France 5 Department of Oncology, Lausanne University Hospital, Lausanne, Switzerland 6 Universite Claude Bernard Lyon 1, Centre de recherche en cancerologie de Lyon, Lyon, France 7 Department of Innovation and Translational Research, Centre Leon Berard, Lyon, France * Co-last authors Correspondence to: Laurence de Leval, email: laurence.deleval@chuv.ch Keywords: CD73; ecto-5'-nucleotidase; immunohistochemistry; melanoma; prognosis Received: February 12, 2018      Accepted: April 30, 2018      Published: June 01, 2018 ABSTRACT Background: CD73 is an ectoenzyme involved in the production of adenosine. It exerts immunosuppressive and protumoral roles and has emerged as a potential immuno-oncology target. Results: CD73 expression was detected in TC in 54% of melanoma metastases, involving 37.5 or intensity > 1) significantly correlated to decreased overall survival (OS) from biopsy. Of the samples containing TIMC, 35% presented CD73+ TIMC. Highly infiltrated tumors were more likely to contain CD73+ TIMC. CD73 expression in TIMC (percentage ≥1%) significantly correlated with improved OS from biopsy. Conclusions: Immunohistochemistry detected CD73 expression in more than half of metastatic melanomas. While CD73 expression in TC significantly correlated with decreased OS, CD73 expression in TIMC significantly associated with improved OS. These results encourage the study of anti-CD73 therapies for metastatic melanoma patients. Methods: CD73 expression was assessed by immunohistochemistry in metastatic melanomas from 114 patients. Immunostainings were evaluated in tumor cells (TC) (percentage, intensity (1–3) and H-score) and in tumor-infiltrating mononuclear cells (TIMC) (percentage).