Clinicopathological analysis of programmed cell death 1 and programmed cell death ligand 1 expression in the tumour microenvironments of diffuse large B cell lymphomas

Histopathology. 2016 Jun;68(7):1079-89. doi: 10.1111/his.12882. Epub 2015 Dec 1.


Aims: To investigate the clinicopathological characteristics of programmed cell death ligand 1 (PD-L1) and programmed cell death 1 (PD-1) expression in the tumour microenvironments of diffuse large B cell lymphoma (DLBCL).

Methods and results: Tumour tissues from 126 DLBCL patients were immunostained for PD-L1 and PD-1. The expression of PD-L1 by tumour cells and/or tumour-infiltrating immune cells (mainly macrophages) was evaluated, and the number of tumour-infiltrating PD-1(+) cells was assessed. PD-L1 expression in tumour cells was observed in 61.1% of DLBCLs, with a weak intensity in 29.4%, moderate intensity in 21.4% and strong intensity in 10.3% of cases. Strong PD-L1 expression in tumour cells was associated significantly with the presence of B symptoms (adjusted P = 0.005) and Epstein-Barr virus (EBV) infection (adjusted P = 0.015), and tended to be higher in activated B cell-like immunophenotype (16.7%) than germinal centre B cell-like immunophenotype (2.5%) (adjusted P = 0.271). DLBCLs with PD-L1 expression in tumour cells/macrophages showed similar clinicopathological characteristics. The quantity of PD-1(+) tumour-infiltrating lymphocytes correlated positively with the level of PD-L1 expression in tumour cells (P = 0.042) or in tumour cells/macrophages (P = 0.03). Increased infiltration of PD-1(+) cells was associated with prolonged progression-free survival (P = 0.005) and overall survival (P = 0.026) in DLBCL patients treated with rituximab-cyclophosphamide, doxorubicin, vincristine, prednisone (R-CHOP), whereas PD-L1 expression had no prognostic significance.

Conclusions: PD-L1 and PD-1 were expressed variably in DLBCLs by tumour cells and tumour-infiltrating immune cells and might be potential therapeutic targets using PD-1/PD-L1 blockade.

Keywords: diffuse large B cell lymphoma; immunotherapy; programmed cell death 1; programmed cell death 1 ligand 1; tumour-associated macrophages.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • B7-H1 Antigen / metabolism*
  • Child
  • Disease-Free Survival
  • Female
  • Gene Expression Regulation, Neoplastic
  • Herpesvirus 4, Human / isolation & purification*
  • Humans
  • Kaplan-Meier Estimate
  • Lymphocytes, Tumor-Infiltrating / metabolism
  • Lymphocytes, Tumor-Infiltrating / pathology
  • Lymphoma, Large B-Cell, Diffuse / diagnosis*
  • Lymphoma, Large B-Cell, Diffuse / metabolism
  • Lymphoma, Large B-Cell, Diffuse / pathology
  • Macrophages / metabolism
  • Macrophages / pathology
  • Male
  • Middle Aged
  • Prognosis
  • Programmed Cell Death 1 Receptor / metabolism*
  • Tumor Microenvironment*
  • Young Adult


  • B7-H1 Antigen
  • CD274 protein, human
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor