Immune system evasion by peripheral nerve sheath tumor

Neurosci Lett. 2006 Apr 10-17;397(1-2):126-9. doi: 10.1016/j.neulet.2005.12.027. Epub 2006 Jan 6.

Abstract

Mechanisms by which tumor cells evade detection by the host's immune system are thought to play a role in progression to malignancy, but this has not been investigated in the context of neurofibromatosis type 1 (NF1). NF1 is an autosomal dominant disorder, in which aggressive peripheral nerve tumors, known as malignant peripheral nerve sheath tumors (MPNSTs), develop in 5-10% of patients. Large scale gene expression profiling of a MPNST-derived cell line, T265, and normal human Schwann cells (hSCs) identified a large group of immune function genes down-regulated in T265 cells. Here we report that the aberrant expression of immune system related genes extends beyond MHC class I and II genes in T265 cells to include a transcription factor (MHC2TA) and other critical components of the antigen processing and presentation apparatus. TAP1, the transporter-activator protein that loads peptide antigens onto MHC class I molecules, is down-regulated, and CD74, a chaperone protein whose function is in processing and transport of MHC class II molecules, is down-regulated and alternatively spliced to produce an RNA transcript not evident in normal human Schwann cells. These findings reveal multiple molecular pathways and at least two cellular mechanisms acting to reduce the normal immune system molecules involved in antigen processing and presentation in cells derived from a peripheral nerve sheath tumor. Acquiring a "silent" immune signature may be a critical step in the progress towards malignancy in MPNSTs.

Publication types

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

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 2
  • ATP-Binding Cassette Transporters / genetics
  • ATP-Binding Cassette Transporters / metabolism
  • Antigens, Differentiation, B-Lymphocyte / metabolism
  • Blotting, Northern / methods
  • Blotting, Western / methods
  • Cell Line, Tumor
  • Gene Expression Regulation, Neoplastic / physiology*
  • Histocompatibility Antigens Class II / metabolism
  • Humans
  • Immune System / metabolism*
  • Immune System / physiopathology
  • Microarray Analysis / methods
  • Nerve Sheath Neoplasms / immunology*
  • Peripheral Nervous System Neoplasms / immunology*
  • RNA, Messenger / biosynthesis
  • Reverse Transcriptase Polymerase Chain Reaction / methods

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 2
  • ATP-Binding Cassette Transporters
  • Antigens, Differentiation, B-Lymphocyte
  • Histocompatibility Antigens Class II
  • RNA, Messenger
  • TAP1 protein, human
  • invariant chain