Combined Genetic Inactivation of β2-Microglobulin and CD58 Reveals Frequent Escape From Immune Recognition in Diffuse Large B Cell Lymphoma

Cancer Cell. 2011 Dec 13;20(6):728-40. doi: 10.1016/j.ccr.2011.11.006. Epub 2011 Dec 1.

Abstract

We report that diffuse large B cell lymphoma (DLBCL) commonly fails to express cell-surface molecules necessary for the recognition of tumor cells by immune-effector cells. In 29% of cases, mutations and deletions inactivate the β2-Microglobulin gene, thus preventing the cell-surface expression of the HLA class-I (HLA-I) complex that is necessary for recognition by CD8(+) cytotoxic T cells. In 21% of cases, analogous lesions involve the CD58 gene, which encodes a molecule involved in T and natural killer cell-mediated responses. In addition to gene inactivation, alternative mechanisms lead to aberrant expression of HLA-I and CD58 in >60% of DLBCL. These two events are significantly associated in this disease, suggesting that they are coselected during lymphomagenesis for their combined role in escape from immune-surveillance.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD58 Antigens / genetics*
  • CD58 Antigens / immunology
  • CD58 Antigens / metabolism
  • Cell Line, Tumor
  • Coculture Techniques
  • Cytotoxicity, Immunologic
  • DNA Copy Number Variations
  • DNA Mutational Analysis
  • Genetic Association Studies
  • Genotype
  • Histocompatibility Antigens Class I / genetics
  • Histocompatibility Antigens Class I / metabolism
  • Humans
  • Killer Cells, Natural / physiology
  • Lymphoma, Large B-Cell, Diffuse / genetics
  • Lymphoma, Large B-Cell, Diffuse / immunology*
  • Mutation*
  • Polymorphism, Single Nucleotide
  • Protein Stability
  • Transcription, Genetic
  • beta 2-Microglobulin / genetics*
  • beta 2-Microglobulin / metabolism

Substances

  • CD58 Antigens
  • Histocompatibility Antigens Class I
  • beta 2-Microglobulin

Associated data

  • GEO/GSE12195