Programmed Cell Death 1 and Programmed Cell Death Ligands in Extranodal Natural Killer/T Cell Lymphoma: Expression Pattern and Potential Prognostic Relevance

Acta Haematol. 2020;143(1):78-88. doi: 10.1159/000500974. Epub 2019 Jul 22.

Abstract

The programmed cell death 1/programmed cell death ligands (PD-1/PD-Ls) axis is a potential immune escape mechanism of cancers. However, data on the PD-1/PD-Ls pathway in EBV-associated extranodal natural killer/T cell lymphoma (ENKTL) and its clinical implication are limited. Herein, we characterized PD-1/PD-L expression and its prognosis relevance in 49 ENKTL patients in Thailand. PD-L1 was expressed frequently on both lymphoma cells (61.2%) and stroma (77.5%), whereas PD-L2 expression was more common on lymphoma (63.2%) than stromal cells. PD-1 was positive in 20.5% of stroma, but undetectable on lymphoma cells. There was no association between baseline clinical characteristics and the expression PD-1/PD-Ls. The survival of patients with PD-Ls on tumor cells was poor. For PD-L1-positive versus negative cases, the 2-year event-free survival (EFS) was 42.2 versus 71.8% (p = 0.03) and 2-year overall survival (OS) was 45.4 versus 78.9% (p = 0.02), respectively. Comparing between patients with PD-L2-positive and PD-L2-negative lymphoma, the 2-year EFS was 37.1 versus 82.4% (p = 0.02) and 2-year OS was 45.2 versus 82.4% (p = 0.03), respectively. Neither PD-1 nor PD-Ls expression in the stroma predicted outcomes. In conclusion, PD-Ls were frequently expressed on ENKTL cells and associated with inferior outcomes. Therefore, PD-Ls are potential prognostic biomarkers and the roles of immune checkpoint blockade therapy in ENKTL deserve further investigation.

Keywords: Extranodal NK/T cell lymphoma; Immune checkpoint; Programmed cell death.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antineoplastic Agents / therapeutic use
  • B7-H1 Antigen / metabolism*
  • Biomarkers, Tumor / metabolism
  • DNA, Viral / blood
  • Female
  • Herpesvirus 4, Human / genetics
  • Humans
  • Lymphoma, Extranodal NK-T-Cell / diagnosis*
  • Lymphoma, Extranodal NK-T-Cell / drug therapy
  • Lymphoma, Extranodal NK-T-Cell / mortality
  • Male
  • Middle Aged
  • Prognosis
  • Programmed Cell Death 1 Ligand 2 Protein / metabolism*
  • Programmed Cell Death 1 Receptor / metabolism*
  • Progression-Free Survival
  • Proportional Hazards Models
  • Survival Rate
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • B7-H1 Antigen
  • Biomarkers, Tumor
  • CD274 protein, human
  • DNA, Viral
  • PDCD1 protein, human
  • PDCD1LG2 protein, human
  • Programmed Cell Death 1 Ligand 2 Protein
  • Programmed Cell Death 1 Receptor