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

Abstract

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.

• Authors: Dohee Kwon, Sehui Kim, Pil-Jong Kim, Heounjeong Go, Soo Jeong Nam, Jin Ho Paik, Young A Kim, Tae Min Kim, Dae Seog Heo, Chul Woo Kim, Yoon Kyung Jeon
• Journal: Histopathology (Histopathology) Vol. 68 Issue 7 Pg. 1079-89 (Jun 2016) ISSN: 1365-2559 [Electronic] England
• PMID: 26426431 (Publication Type: Journal Article)
• Copyright: © 2015 John Wiley & Sons Ltd.

Chemical References

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

Topics

• 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, pathology)
• Lymphoma, Large B-Cell, Diffuse (diagnosis, metabolism, pathology)
• Macrophages (metabolism, pathology)
• Male
• Middle Aged
• Prognosis
• Programmed Cell Death 1 Receptor (metabolism)
• Tumor Microenvironment
• Young Adult