B7-H1 (PD-L1, CD274) suppresses host immunity in T-cell lymphoproliferative disorders

Blood. 2009 Sep 3;114(10):2149-58. doi: 10.1182/blood-2009-04-216671. Epub 2009 Jul 13.

Abstract

Stromal elements present within the tumor microenvironment may suppress host immunity and promote the growth of malignant lymphocytes in B cell-derived non-Hodgkin lymphoma (NHL). In contrast, little is known about the microenvironment's role in T cell-derived NHL. B7-H1 (PD-L1, CD274), a member of the B7 family of costimulatory/co-inhibitory ligands expressed by both malignant cells and stromal cells within the tumor microenvironment, has emerged as an important immune modulator capable of suppressing host immunity. Therefore, B7-H1 expression and function were analyzed in cutaneous and peripheral T-cell NHL. B7-H1 was expressed by tumor cells, monocytes, and monocyte-derived cells within the tumor microenvironment in T-cell NHL and was found to inhibit T-cell proliferation and promote the induction of FoxP3(+) regulatory T cells. Collectively, the data presented provide the first evidence implicating B7-H1 in the suppression of host immunity in T-cell lymphoproliferative disorders and suggest that the targeting of B7-H1 may represent a novel therapeutic approach.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Antigens, CD / biosynthesis
  • Antigens, CD / immunology*
  • B7-H1 Antigen
  • Cell Line, Tumor
  • Cell Proliferation
  • Forkhead Transcription Factors
  • Gene Expression Regulation, Neoplastic / immunology*
  • Humans
  • Immune Tolerance*
  • Lymphoproliferative Disorders / immunology*
  • Lymphoproliferative Disorders / metabolism
  • Lymphoproliferative Disorders / therapy
  • Monocytes / immunology
  • Monocytes / metabolism
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / metabolism

Substances

  • Antigens, CD
  • B7-H1 Antigen
  • CD274 protein, human
  • FOXP3 protein, human
  • Forkhead Transcription Factors