CD137 is expressed in follicular dendritic cell tumors and in classical Hodgkin and T-cell lymphomas: diagnostic and therapeutic implications

Am J Pathol. 2012 Sep;181(3):795-803. doi: 10.1016/j.ajpath.2012.05.015.

Abstract

CD137 (also known as 4-1BB and TNFRSF9) is a member of the tumor necrosis factor receptor superfamily. Originally identified as a costimulatory molecule expressed by activated T cells and NK cells, CD137 is also expressed by follicular dendritic cells, monocytes, mast cells, granulocytes, and endothelial cells. Anti-CD137 immunotherapy has recently shown promise as a treatment for solid tumors and lymphoid malignancies in preclinical models. We defined the expression of CD137 protein in both normal and neoplastic hematolymphoid tissue. CD137 protein is expressed by follicular dendritic cells in the germinal center and scattered paracortical T cells, but not by normal germinal-center B cells, bone marrow progenitor cells, or maturing thymocytes. CD137 protein is expressed by a select group of hematolymphoid tumors, including classical Hodgkin lymphoma, T-cell and NK/T-cell lymphomas, and follicular dendritic cells neoplasms. CD137 is a novel diagnostic marker of these tumors and suggests a possible target for tumor-directed antibody therapy.

Publication types

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

MeSH terms

  • Biomarkers, Tumor / metabolism
  • Dendritic Cells, Follicular / metabolism
  • Dendritic Cells, Follicular / pathology
  • Flow Cytometry
  • Histiocytic Disorders, Malignant / diagnosis*
  • Histiocytic Disorders, Malignant / metabolism*
  • Histiocytic Disorders, Malignant / pathology
  • Histiocytic Disorders, Malignant / therapy
  • Hodgkin Disease / diagnosis
  • Hodgkin Disease / metabolism*
  • Hodgkin Disease / pathology
  • Hodgkin Disease / therapy*
  • Humans
  • Immunohistochemistry
  • Lymphocyte Subsets / metabolism
  • Lymphoid Tissue / metabolism
  • Lymphoid Tissue / pathology
  • Lymphoma, B-Cell / metabolism
  • Lymphoma, B-Cell / pathology
  • Lymphoma, T-Cell / diagnosis*
  • Lymphoma, T-Cell / metabolism*
  • Lymphoma, T-Cell / pathology
  • Lymphoma, T-Cell / therapy
  • Tumor Necrosis Factor Receptor Superfamily, Member 9 / metabolism*

Substances

  • Biomarkers, Tumor
  • TNFRSF9 protein, human
  • Tumor Necrosis Factor Receptor Superfamily, Member 9