Elsevier

Neuroscience Letters

Volume 397, Issues 1–2, 10–17 April 2006, Pages 126-129
Neuroscience Letters

Immune system evasion by peripheral nerve sheath tumor

https://doi.org/10.1016/j.neulet.2005.12.027Get rights and content

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.

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Acknowledgements

We would like to thank George DeVries and Robert Farrer for normal human Schwann cells and the T265 cell line. We would also like to thank Kevin Becker and Bill Wood, NIA Gene Expression and Genomics unit for providing the cDNA microarrays, and Nancy Ratner for helpful discussions. This work was supported by the National Institute of Child Health and Human Development.

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