Abstract
Programmed cell death 1 (PD-1)/PD-1 ligand 1 (PD-L1) pathway blockade has emerged as a promising strategy for cancer therapy. Extranodal natural killer/T cell lymphoma (ENKTL) is an aggressive disease characterized by a strong association with Epstein–Barr virus (EBV), and chronic EBV infection is known to induce PD-L1 expression. However, the PD-1/PD-L1 pathway status in ENKTL remains elusive. Thus, the expression pattern of PD-1 and PD-L1 was investigated in 73 ENKTL cases, and its clinicopathological features and prognostic significance were analyzed. Most ENKTLs had few PD-1+ lymphocytes in the tumor microenvironment. PD-L1 was positive in 56 % (n = 41/73) with a cutoff value of ≥10 % of tumor cells and in 62 % (n = 45/73) with a cutoff value of ≥10 % of total cells including malignant and non-malignant cells. PD-L1 expression on tumor cells was mostly correlated with PD-L1 expression on non-malignant cells. PD-L1 positivity showed no significant relationship with clinicopathological features. However, patients with PD-L1+ ENKTL exhibited better 5-year overall survival (OS) and a trend for longer 5-year progression-free survival. Moreover, in the subgroups with clinically advanced parameters including late stage III/IV, higher International Prognostic Index scores of 2–5 or non-upper aerodigestive tract involvement PD-L1 positivity was also associated with favorable OS. PD-L1 expression was the only significant independent predictor for longer OS in patients with advanced stage (III/IV) ENKTL. These results suggest that PD-L1 might be used as a novel prognostic marker.
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Acknowledgments
This work was supported by a grant from the National Research Foundation of Korea (NRF) (NRF-2013R1A1A2013210) funded by Ministry of Education, Science, and Technology (MEST) and a grant from the Global Core Research Center (GCRC) (No. 2012-0001190) funded by Ministry of Science, ICT, and Future Planning (MSIP), Republic of Korea.
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Kim, W.Y., Jung, H.Y., Nam, S.J. et al. Expression of programmed cell death ligand 1 (PD-L1) in advanced stage EBV-associated extranodal NK/T cell lymphoma is associated with better prognosis. Virchows Arch 469, 581–590 (2016). https://doi.org/10.1007/s00428-016-2011-0
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DOI: https://doi.org/10.1007/s00428-016-2011-0