title: Programmed death 1 expression in the peritumoral microenvironment is associated with a poorer prognosis in classical Hodgkin lymphoma.
abstract: Programmed cell death protein-1 (PD-1) inhibitor may be therapeutic in patients with relapsed or refractory classical Hodgkin's lymphoma (cHL). This study examined the prognostic significance of PD-1 and two PD-1 ligands (PD-L1 and PD-L2) in uniformly treated cHL. Diagnostic tissues from 109 cHL patients treated with a doxorubicin, bleomycin, vinblastine, and dacarbazine regimen were evaluated retrospectively by immunohistochemical analysis of PD-L1, PD-L2, and PD-1 expressions. The median follow-up time was 4.91 years (range, 0.17-17.33 years). Thirteen patients (11 %) expressed PD-1 protein in the peritumoral microenvironment, which was associated with poor overall survival (OS) (P = 0.017). PD-L1 or PD-L2 expression was not associated with OS. There was no correlation between PD-L1 and PD-1 expression or between PD-L2 and PD-1 expression. Multivariate analysis identified PD-1 protein as an independent prognostic factor for OS (P = 0.019). Subgroup analysis according to the Ann Arbor stage of cHL showed that PD-1 protein expression had a prognostic value in limited-stage cHL (P = 0.048). PD-1 is an independent prognostic factor in cHL and may allow the identification of a subgroup of patients with limited-stage cHL who require more intensive therapy and who may benefit from anti-PD-1 agents.
authors.affiliation: Department of Pathology, Ajou University School of Medicine, Suwon, South Korea.
authors.forename: Young Wha
authors.initials: YW
authors.lastname: Koh
authors.affiliation: Department of Pathology, Seoul National University Hospital, Seoul, South Korea.
authors.forename: Yoon Kyung
authors.initials: YK
authors.lastname: Jeon
authors.affiliation: Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
authors.forename: Dok Hyun
authors.initials: DH
authors.lastname: Yoon
authors.affiliation: Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea.
authors.forename: Cheolwon
authors.initials: C
authors.lastname: Suh
authors.affiliation: Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Seoul, 138-736, South Korea. jrhuh@amc.seoul.kr.
authors.forename: Jooryung
authors.initials: J
authors.lastname: Huh
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D060890:B7-H1 Antigen / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001761:Bleomycin / Q000008:administration & dosage; D003606:Dacarbazine / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D005500:Follow-Up Studies; D006689:Hodgkin Disease / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D061027:Programmed Cell Death 1 Ligand 2 Protein / Q000378:metabolism*; D061026:Programmed Cell Death 1 Receptor / Q000378:metabolism*; D012189:Retrospective Studies; D015996:Survival Rate; D059016:Tumor Microenvironment / Q000187:drug effects*; D014747:Vinblastine / Q000008:administration & dosage; D055815:Young Adult
chemical_list: D060890:B7-H1 Antigen; D014408:Biomarkers, Tumor; C423236:CD274 protein, human; C105992:PDCD1 protein, human; C556977:PDCD1LG2 protein, human; D061027:Programmed Cell Death 1 Ligand 2 Protein; D061026:Programmed Cell Death 1 Receptor; D001761:Bleomycin; D014747:Vinblastine; D003606:Dacarbazine; D004317:Doxorubicin
keywords: Hodgkin’s lymphoma; PD-1; PD-L1; PD-L2; Prognosis