PD-L1 mRNA expression in plasma-derived exosomes is associated with response to anti-PD-1 antibodies in melanoma and NSCLC

被引：218

作者：

Del Re, Marzia ^{[1
]}

Marconcini, Riccardo ^{[2
]}

Pasquini, Giulia ^{[2
]}

Rofi, Eleonora ^{[1
]}

Vivaldi, Caterina ^{[2
]}

Bloise, Francesco ^{[2
]}

Restante, Giuliana ^{[1
]}

Arrigoni, Elena ^{[1
]}

Caparello, Chiara ^{[2
]}

Bianco, Maria Grazia ^{[2
]}

Crucitta, Stefania ^{[1
]}

Petrini, Iacopo ^{[3
]}

Vasile, Enrico ^{[2
]}

Falcone, Alfredo ^{[2
]}

Danesi, Romano ^{[1
]}

机构：

[1] Univ Pisa, Dept Clin & Expt Med, Clin Pharmacol & Pharmacogenet Unit, Pisa, Italy

[2] Univ Pisa, Dept Translat Res & New Technol Med & Surg, Med Oncol Unit, Pisa, Italy

[3] Univ Pisa, Dept Translat Res & New Technol Surg & Med, Gen Pathol, Pisa, Italy

来源：

BRITISH JOURNAL OF CANCER | 2018年 / 118卷 / 06期

关键词：

PD-L1; exosomes; circulating nucleic acids; immunotherapy; predictive biomarker; pharmacogenetics; nivolumab; pembrolizumab; CELL LUNG-CANCER; NIVOLUMAB; BLOCKADE;

D O I：

10.1038/bjc.2018.9

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Background: PD-L1 expression in tumour tissues is widely used to select patients to receive anti-PD-1/PD-L1 antibodies, but data are lacking on the correlation of plasma PD-L1 levels with the effect of treatments. Methods: To investigate the association between PD-L1 mRNA in plasma-derived exosomes and response to nivolumab and pembrolizumab in patients with melanoma (n = 18) and NSCLC (n = 8), blood was obtained at time point 0 and after 2 months. Exosomal PD-L1 mRNA was measured by digital droplet PCR. Results: The mean +/- s.e.m. PD-L1 levels in patients with complete and partial responses were 830.4 +/- 231.3 and 242.5 +/- 82.5 copies per ml at time 0 vs 2 months, respectively (P = 0.016). In patients with stable disease the mean +/- s.e.m. values were 298.8 +/- 97.2 vs 247.5 +/- 29.8 copies per ml (P = 0.586), while in progressive disease, PD-L1 mRNA levels were 204.0 +/- 68.8 vs 416.0 +/- 87.8 copies per ml at time 0 vs 2 months, respectively (P = 0.001). Conclusions: This study demonstrates that exosomal PD-L1 is significantly associated with response to treatment.

引用

页码：820 / 824

页数：5

共 12 条

[11] Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer [J].

Rizvi, Naiyer A. ;

Hellmann, Matthew D. ;

Snyder, Alexandra ;

Kvistborg, Pia ;

Makarov, Vladimir ;

Havel, Jonathan J. ;

Lee, William ;

Yuan, Jianda ;

Wong, Phillip ;

Ho, Teresa S. ;

Miller, Martin L. ;

Rekhtman, Natasha ;

Moreira, Andre L. ;

Ibrahim, Fawzia ;

Bruggeman, Cameron ;

Gasmi, Billel ;

Zappasodi, Roberta ;

Maeda, Yuka ;

Sander, Chris ;

Garon, Edward B. ;

Merghoub, Taha ;

Wolchok, Jedd D. ;

Schumacher, Ton N. ;

Chan, Timothy A. .

SCIENCE, 2015, 348 (6230) :124-128

[12] Nivolumab in Previously Untreated Melanoma without BRAF Mutation [J].

Robert, Caroline ;

Long, Georgina V. ;

Brady, Benjamin ;

Dutriaux, Caroline ;

Maio, Michele ;

Mortier, Laurent ;

Hassel, Jessica C. ;

Rutkowski, Piotr ;

McNeil, Catriona ;

Kalinka-Warzocha, Ewa ;

Savage, Kerry J. ;

Hernberg, Micaela M. ;

Lebbe, Celeste ;

Charles, Julie ;

Mihalcioiu, Catalin ;

Chiarion-Sileni, Vanna ;

Mauch, Cornelia ;

Cognetti, Francesco ;

Arance, Ana ;

Schmidt, Henrik ;

Schadendorf, Dirk ;

Gogas, Helen ;

Lundgren-Eriksson, Lotta ;

Horak, Christine ;

Sharkey, Brian ;

Waxman, Ian M. ;

Atkinson, Victoria ;

Ascierto, Paolo A. .

NEW ENGLAND JOURNAL OF MEDICINE, 2015, 372 (04) :320-330

← 1 2 →