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Expression of programmed cell death ligand 1 (PD-L1) in advanced stage EBV-associated extranodal NK/T cell lymphoma is associated with better prognosis

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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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Authors and Affiliations

  1. Department of Pathology, Konkuk University School of Medicine, 120 Neungdong-ro, Hwayang-dong, Gwangjin-gu, Seoul, Republic of Korea

    Wook Youn Kim & Ho Young Jung

  2. Department of Pathology, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, Republic of Korea

    Soo Jeong Nam, Chul-Woo Kim & Yoon Kyung Jeon

  3. The Tumor Immunity Medical Research Center, Cancer Research Center, Seoul National University College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, Republic of Korea

    Wook Youn Kim, Soo Jeong Nam, Chul-Woo Kim & Yoon Kyung Jeon

  4. Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, Republic of Korea

    Tae Min Kim & Dae Seog Heo

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. This study was approved by the Institutional Review Board of Seoul National University Hospital (H-0805-068-245). This article does not contain any studies with animals performed by any of the authors.

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Informed consent for participation in the study was waived by the Institutional Review Board of Seoul National University Hospital on the basis that this study was a retrospective study by using archived material and did not increase risk to the patients.

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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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