A novel approach to rescue immune escape in oral squamous cell carcinoma: Combined use of interferon-γ and LY294002

Wei Han; Hongya Pan; Linlin Jiang; Kuijie Wei; Duohong Zou; Zhiyuan Zhang

A novel approach to rescue immune escape in oral squamous cell carcinoma: Combined use of interferon-γ and LY294002

Oncol Rep. 2011 Jan;25(1):181-7.

Authors

Wei Han¹, Hongya Pan, Linlin Jiang, Kuijie Wei, Duohong Zou, Zhiyuan Zhang

Affiliation

¹ Department of Oral and Maxillofacial Surgery, Ninth People's Hospital, School of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Stomatology and Shanghai Research Institute of Stomatology, Shanghai, P.R. China.

PMID: 21109975

Abstract

Major histocompatibility complex (MHC) class I molecules have been found to be downmodulated in many tumors. The antigen-processing machinery (APM) genes, especially transporters associated with antigen processing (TAP)-1 and tapasin play important roles in the processing of class I antigens. In this study, we investigated the expression of TAP-1 and tapasin in oral squamous cell carcinoma (OSCC); the result indicated significant down-regulation in the expression of these genes. Interferon (IFN)-γ treatment was applied. After the addition of IFN-γ, unexpectedly, the phosphoinositide 3-kinase (PI3K)/AKT signaling pathway was activated, which induced the proliferation of tumor cells. With the combined application of LY294002 (specific inhibitor of AKT signaling) and IFN-γ, tumor cell apoptosis was induced and the expression of TAP-1 and tapasin was still up-regulated. Hence, our method is a novel and efficient approach to use IFN-γ for rescuing the cells from immunosurveillance.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

ATP Binding Cassette Transporter, Subfamily B, Member 2
ATP-Binding Cassette Transporters / biosynthesis
Adult
Aged
Aged, 80 and over
Antineoplastic Combined Chemotherapy Protocols / pharmacology*
Apoptosis / drug effects
Blotting, Western
Carcinoma, Squamous Cell / metabolism*
Carcinoma, Squamous Cell / pathology
Cell Proliferation / drug effects
Chromones / pharmacology
Female
Gene Expression
Gene Expression Profiling
Humans
Interferon-gamma / pharmacology
Male
Membrane Transport Proteins / biosynthesis
Middle Aged
Morpholines / pharmacology
Mouth Neoplasms / metabolism*
Mouth Neoplasms / pathology
Neoplasm Staging
RNA, Messenger / analysis
Reverse Transcriptase Polymerase Chain Reaction
Signal Transduction / drug effects
Tumor Escape / drug effects*

Substances

ATP Binding Cassette Transporter, Subfamily B, Member 2
ATP-Binding Cassette Transporters
Chromones
Membrane Transport Proteins
Morpholines
RNA, Messenger
TAP1 protein, human
tapasin
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
Interferon-gamma