1. ¹Department of Immunology and Infectious Diseases, Shinshu University Graduate School of Medicine, Matsumoto, Nagano, Japan
2. ²Department of Laboratory Medicine, Shinshu University Hospital, Matsumoto, Nagano, Japan

Correspondence: Dr T Hayashi, Department of Immunology and Infectious Diseases, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano 390-8621, Japan. E-mail: takuma-h@sch.md.shinshu-u.ac.jp

Received 18 July 2005; Revised 21 December 2005; Accepted 5 January 2006; Published online 13 February 2006.

Abstract

The presentation of human leukocyte antigens (HLA) class I requires the coordinated expression of numerous components involved in antigen presentation. Tumor cells may alter the antigen presentation by HLA class I, allowing them to evade antitumor immunity. In many cases, the lack of antigen presentation can be attributed to the downregulation of genes needed for antigen processing, such as the transporters associated with antigen processing (TAP) 1, and the proteasomal component, low molecular weight proteins (LMP) 2. The TAP1 and LMP2 genes are transcribed from a shared bidirectional promoter containing an interferon (IFN)--response factor element; thus, the IFN--signal strongly induces both TAP1 and LMP2 expression. Low molecular weight proteins2-deficient mice exhibited the development of uterine leiomyosarcomas. Here, the differential responsiveness to IFN- of the SKN human uterine leiomyosarcomas cell line was investigated. We now identify the G871E mutation in the ATP-binding region of Janus kinases 1, suggesting that the loss of TAP1 and LMP2 induction is a defect in the earliest steps of the IFN--signal pathway, resulting in the inability of SKN cells to upregulate the antigen-processing pathway. Understanding the mechanisms by which these tumors circumvent cytokine signalling, thereby evading antitumor-specific immunity, would greatly aid the efficacy of immunotherapy for treating uterine leiomyosarcomas.