{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T18:08:17Z","timestamp":1791396497781,"version":"4.3.3"},"reference-count":33,"publisher":"BMJ","issue":"2","license":[{"start":{"date-parts":[[2020,12,23]],"date-time":"2020-12-23T00:00:00Z","timestamp":1608681600000},"content-version":"unspecified","delay-in-days":22,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002345","name":"Eberhard Karls Universit\u00e4t T\u00fcbingen","doi-asserted-by":"publisher","award":["2509-0-0"],"award-info":[{"award-number":["2509-0-0"]}],"id":[{"id":"10.13039\/501100002345","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007316","name":"Klaus Tschira Stiftung","doi-asserted-by":"publisher","award":["00.316.2017"],"award-info":[{"award-number":["00.316.2017"]}],"id":[{"id":"10.13039\/501100007316","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003852","name":"Regione Campania","doi-asserted-by":"publisher","award":["POR Campania FESR 2007-2013 OO2.1-Ockey"],"award-info":[{"award-number":["POR Campania FESR 2007-2013 OO2.1-Ockey"]}],"id":[{"id":"10.13039\/501100003852","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","award":["Ricerca corrente M2\/M"],"award-info":[{"award-number":["Ricerca corrente M2\/M"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Immunother Cancer"],"accepted":{"date-parts":[[2020,11,27]]},"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Inhibitors of immune checkpoint programmed cell death protein 1 (PD-1) receptor on T cells have shown remarkable clinical outcomes in metastatic melanoma. However, most patients are resistant to therapy. Production of extracellular adenosine, via CD73-mediated catabolism of AMP, contributes to suppress T-cell-mediated responses against cancer. In this study, we analyzed the expression and activity of soluble CD73 in sera of patients with melanoma undergoing anti-PD-1\u00b1 cytotoxic T-lymphocyte-associated antigen 4 therapy.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Soluble CD73 expression and activity were retrospectively analyzed in serum of a total of 546 patients with melanoma from different centers before starting treatment (baseline) with anti-PD-1 agents, nivolumab or pembrolizumab, and compared with those of 96 healthy subjects. The CD73 activity was correlated with therapy response and survival of patients.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Patients with melanoma show significantly higher CD73 activity and expression than those observed in healthy donors (p&lt;0.0001). Elevated pretreatment levels of CD73 activity were associated with non-response to therapy with nivolumab or pembrolizumab. During treatment, levels of soluble CD73 activity remain unchanged from baseline and still stratify clinical responders from non-responders. High levels of serum CD73 enzymatic activity associate with reduced overall survival (OS; HR=1.36, 95% CI 1.03 to 1.78; p=0.03) as well as progression-free survival (PFS; HR=1.42, 95% CI 1.13 to 1.79, p=0.003). Further, the multivariate Cox regression analysis indicates that serum CD73 activity is an independent prognostic factor besides serum lactate dehydrogenase levels and the presence of brain metastases for both OS (p=0.009) and PFS (p=0.001).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Our data indicate the relevance of serum CD73 in patients with advanced melanoma receiving anti-PD-1 therapy and support further investigation on targeting CD73 in combination with anti-PD-1 antibodies.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/jitc-2020-001689","type":"journal-article","created":{"date-parts":[[2020,12,23]],"date-time":"2020-12-23T16:49:48Z","timestamp":1608742188000},"page":"e001689","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":49,"title":["Serum CD73 is a prognostic factor in patients with metastatic melanoma and is associated with response to anti-PD-1 therapy"],"prefix":"10.1136","volume":"8","author":[{"given":"Roberta","family":"Turiello","sequence":"first","affiliation":[{"name":"Pharmacy, University of Salerno, Fisciano, Campania, Italy"},{"name":"PhD Program in Drug Discovery and Development, University of Salerno, Fisciano, Campania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariaelena","family":"Capone","sequence":"additional","affiliation":[{"name":"Istituto Nazionale Tumori IRCCS Fondazione Pascale, Napoli, Campania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana","family":"Giannarelli","sequence":"additional","affiliation":[{"name":"Biostatistic Unit, Regina Elena Institute, Roma, Lazio, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elva","family":"Morretta","sequence":"additional","affiliation":[{"name":"Pharmacy, University of Salerno, Fisciano, Campania, 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