Abstract | BACKGROUND: METHODS: 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. RESULTS: Patients with melanoma show significantly higher CD73 activity and expression than those observed in healthy donors (p<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). CONCLUSION: 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.
|
Authors | Roberta Turiello, Mariaelena Capone, Diana Giannarelli, Elva Morretta, Maria Chiara Monti, Gabriele Madonna, Domenico Mallardo, Lucia Festino, Rosa Azzaro, Mitchell P Levesque, Laurence Imhof, Benjamin Weide, Teresa Amaral, Marc Chevrier, Antje Sucker, Piotr Rutkowski, Dirk Schadendorf, Celeste Lebbe, Jason John Luke, Kilian Wistuba-Hamprecht, Reinhard Dummer, Aldo Pinto, Silvana Morello, Paolo A Ascierto |
Journal | Journal for immunotherapy of cancer
(J Immunother Cancer)
Vol. 8
Issue 2
(12 2020)
ISSN: 2051-1426 [Electronic] England |
PMID | 33361405
(Publication Type: Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
|
Copyright | © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. |
Chemical References |
- Biomarkers, Tumor
- GPI-Linked Proteins
- Immune Checkpoint Inhibitors
- 5'-Nucleotidase
- NT5E protein, human
|
Topics |
- 5'-Nucleotidase
(blood)
- Adult
- Aged
- Aged, 80 and over
- Biomarkers, Tumor
(blood)
- Female
- GPI-Linked Proteins
(blood)
- Humans
- Immune Checkpoint Inhibitors
(therapeutic use)
- Immunotherapy
(methods)
- Male
- Melanoma
(blood, drug therapy)
- Middle Aged
- Prognosis
- Retrospective Studies
- Young Adult
|