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Del Re, Marzia; Vivaldi, Caterina; Rofi, Eleonora; Salani, Francesca; Crucitta, Stefania; Catanese, Silvia; Fontanelli, Lorenzo; Massa, Valentina; Cucchiara, Federico; Fornaro, Lorenzo; Capuano, Annalisa; Fogli, Stefano; Vasile, Enrico; Danesi, Romano
Cancers, 07/2021, Volume: 13, Issue: 15Journal Article
Pancreatic ductal adenocarcinoma (PDAC) is a non-immunogenic tumor poorly responsive to immune checkpoint inhibitors. This study investigates the effect of 5-fluorouracil (5-FU), irinotecan, and oxaliplatin (FOLFIRINOX), and gemcitabine plus nab-paclitaxel (GEMnPAC) regimens on PD-L1 mRNA expression in plasma-derived microvesicles (MVs) in 50 PDAC patients. Plasma was collected before starting chemotherapy and after 3 months of treatment. mRNA was extracted from MVs, and PD-L1 expression was measured by digital droplet PCR. Twenty-eight patients were PD-L1 positive in MVs at baseline, of which 18 were in the GEMnPAC cohort and 10 in the FOLFIRINOX one. The amount of PD-L1 expression in MVs increased from baseline to 3 months of treatment in patients receiving GEMnPAC (median value 0.002 vs. 0.005; = 0.01) compared to those treated with FOLFIRINOX (median 0.003 vs. 0.004; = 0.97). The increase in PD-L1 mRNA expression in MVs was not related to tumor response (PR + SD: = 0.08; PD: = 0.28). Our findings demonstrate that GEMnPAC can increase PD-L1 mRNA expression in patient-derived circulating MVs, providing a rationale for testing the efficacy of this regimen in sequential or simultaneous combinations with immunotherapy in PDAC patients.
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