1. Frequency of circulating CD8+CD73+T cells is associated with survival in nivolumab-treated melanoma patients.
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Capone, Mariaelena, Fratangelo, Federica, Giannarelli, Diana, Sorrentino, Claudia, Turiello, Roberta, Zanotta, Serena, Galati, Domenico, Madonna, Gabriele, Tuffanelli, Marilena, Scarpato, Luigi, Grimaldi, Antonio M., Esposito, Assunta, Azzaro, Rosa, Pinto, Antonio, Cavalcanti, Ernesta, Pinto, Aldo, Morello, Silvana, and Ascierto, Paolo A.
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MELANOMA ,T cells ,FLOW cytometry ,BRAF genes ,LYMPHOCYTES ,CELLS ,INTERLEUKIN-7 - Abstract
Background: PD-1 blocking agents, such as nivolumab, have demonstrated clear anti-tumor effects and clinical benefits in a subset of patients with advanced malignancies. Nonetheless, more efforts are needed to identify reliable biomarkers for outcome, to correctly select patients who will benefit from anti-PD-1 treatment. The aim of this study was to investigate the role of peripheral CD8+T cells expressing CD73, involved in the generation of the immune suppressive molecule adenosine, in predicting outcome after nivolumab treatment in advanced melanoma patients.Methods: PBMCs from 100 melanoma patients treated with nivolumab were collected at National Cancer Institute "G. Pascale" of Naples. Frequencies of CD8+ lymphocytes phenotypes were assessed by flow cytometry at baseline before nivolumab treatment, along with clinical characteristics and blood count parameters. Healthy controls (n = 20) were also analysed. Percentages of baseline T cells expressing PD-1 and CD73 were correlated with outcome after nivolumab treatment.Results: Melanoma patients presented a lower frequency of total circulating CD8+ lymphocytes than control subjects (p = 0.008). Patients with low baseline percentage of circulating CD8+PD-1+CD73+ lymphocytes (< 2.3%) had better survival (22.4 months vs 6.9 months, p = 0.001). Patients (39%) with clinical benefit from nivolumab therapy presented a significantly lower frequency of circulating CD8+PD-1+CD73+ lymphocytes than patients who progressed to nivolumab treatment (p = 0.02).Conclusions: Our observations suggest that baseline CD73 expression on circulating CD8+PD-1+ lymphocytes appear a promising biomarker of response to anti-PD-1 treatment in melanoma patients. Further investigations are needed for validation and for clarifying its role as prognostic or predictive marker. [ABSTRACT FROM AUTHOR]- Published
- 2020
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