CD73 expression and clinical significance in human metastatic melanoma.

Inês Monteiro,Mohamed Faouzi,Olivier Michielin,Christine Ménétrier-Caux,Laurence De Leval,Selena Vigano,Pedro Romero,Christophe Caux,Isabelle Treilleux

doi:10.18632/oncotarget.25426

Abstract

BackgroundCD73 is an ectoenzyme involved in the production of adenosine. It exerts immunosuppressive and protumoral roles and has emerged as a potential immuno-oncology target.ResultsCD73 expression was detected in TC in 54% of melanoma metastases, involving < 50% TC in the majority of the cases, with variable intensity. CD73 expression was significantly associated with a lower Breslow's depth of the primary lesion and was more frequent in patients having received prior non-surgical therapies. In an adjusted analysis, CD73 expression in TC (H-score > 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.ConclusionsImmunohistochemistry 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.MethodsCD73 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).

Highlights

CD73 is an ectoenzyme with a 5′-nucleotidase activity, which catalyzes the rate-limiting step in the generation of extracellular adenosine [1,2,3]
CD73 expression was detected in tumor cells (TC) in 54% of melanoma metastases, involving < 50% TC in the majority of the cases, with variable intensity
While CD73 expression in TC significantly correlated with decreased overall survival (OS), CD73 expression in tumor-infiltrating mononuclear cells (TIMC) significantly associated with improved OS

Summary

Introduction

CD73 is an ectoenzyme with a 5′-nucleotidase activity, which catalyzes the rate-limiting step in the generation of extracellular adenosine [1,2,3]. CD73 expression and function is increased by hypoxic conditions and several inflammatory mediators [1]. CD73 participates in the catabolism of extracellular ATP which is first converted by the ectoenzyme CD39 to ADP and AMP, the latter being transformed to adenosine by CD73 [3]. Hypoxia or inflammation, extracellular adenosine levels increase [1]. In these circumstances, adenosine down-regulates inflammatory and immune responses, modulating the amplitude of physiological responses and preventing collateral tissue damage [3]. 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

Methods

Results

Conclusion