Programmed cell death 1 expression is associated with inferior survival in patients with primary central nervous system lymphoma

Abstract

// Hyunsoo Cho 1, 2, * , Se Hoon Kim 3, * , Soo-Jeong Kim 1 , Jong Hee Chang 4 , Woo-Ick Yang 3 , Chang-Ok Suh 5 , Yu Ri Kim 1 , Ji Eun Jang 1 , June-Won Cheong 1 , Yoo Hong Min 1 and Jin Seok Kim 1 1 Division of Hematology, Department of Internal Medicine, Yonsei University College of Medicine, Severance Hospital, Seoul 03722, Republic of Korea 2 Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon 34141, Republic of Korea 3 Department of Pathology, Yonsei University College of Medicine, Severance Hospital, Seoul 03722, Republic of Korea 4 Department of Neurosurgery, Yonsei University College of Medicine, Severance Hospital, Seoul 03722, Republic of Korea 5 Department of Radiation Oncology, Yonsei University College of Medicine, Severance Hospital, Seoul 03722, Republic of Korea * These authors have contributed equally to this work Correspondence to: Jin Seok Kim, email: hemakim@yuhs.ac Keywords: primary central nervous system lymphoma, programmed cell death 1, programmed cell death-ligand 1, programmed cell death-ligand 2, prognosis Received: June 12, 2017      Accepted: July 13, 2017      Published: August 14, 2017 ABSTRACT Programmed cell death 1 (PD-1) and its ligands PD-L1/PD-L2 have been shown to mediate immune evasion in various cancers, but their prognostic implications in patients with primary central nervous system lymphoma (PCNSL) are poorly understood. Therefore, we analyzed 76 PCNSL patients at initial diagnosis who were treated homogenously with high-dose methotrexate-based chemotherapy, and evaluated the prognostic roles of high immunohistochemical PD-1, PD-L1, and PD-L2 expression. The cut-off values for high PD-1 (≥ 70 cells/high power field [HPF]), PD-L1 (≥ 100 cells/HPF), and PD-L2 (≥ 100 cells/HPF) were determined by the area under the receiver operating characteristic curve. Expression of PD-1, PD-L1, and PD-L2 was high in 7.9%, 13.2%, and 42.1% patients, respectively. High PD-1, ( P = 0.007) and Memorial Sloan Kettering Cancer Center (MSKCC) prognostic scoring ( P = 0.019) were independently associated with inferior overall survival on multivariate analysis. High PD-1 also remained an independent prognostic factor for inferior progression-free survival ( P = 0.028), as did MSKCC prognostic scoring ( P = 0.041) on multivariate analysis. However, there were no differences in survival according to the expression levels of PD-L1/PD-L2 in PCNSL tumor microenvironment. Our results suggest that PD-1 may be considered a biomarker and potential therapeutic target in PCNSL.