This Article Full Text Full Text (PDF) All Versions of this Article: 0008-5472.CAN-08-4311v1 69/13/5505    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Dibra, D. Articles by Li, S. PubMed PubMed Citation Articles by Dibra, D. Articles by Li, S.

Expression of WSX1 in Tumors Sensitizes IL-27 Signaling-Independent Natural Killer Cell Surveillance

¹ Department of Comparative Biomedical Sciences, Louisiana State University, Baton Rouge, Louisiana and ² Department of Pathology, Temple University School of Medicine, Philadelphia, Pennsylvania

Requests for reprints: Shulin Li, Department of Comparative Biomedical Sciences, Louisiana State University, Skip Bertman Drive, Baton Rouge, LA 70803. Phone: 225-578-9035; Fax: 225-578-9895; E-mail: sli{at}vetmed.lsu.edu.

Key Words: innate immunity • NK cell • IL-27 • interleukin • TCCR • tumor • WSX1

It is well known that the interleukin (IL)-27 receptor WSX1 is expressed in immune cells and induces an IL-27–dependent immune response. Opposing this conventional dogma, this study reveals a much higher level of WSX1 expression in multiple types of epithelial tumor cells when compared with normal epithelial cells. Expression of exogenous WSX1 in epithelial tumor cells suppresses tumorigenicity in vitro and inhibits tumor growth in vivo. Different from the role of WSX1 in immune cells, the antitumor activity of WSX1 in epithelial tumor cells is independent of IL-27 signaling but is mainly dependent on natural killer (NK) cell surveillance. Deficiency of either the IL-27 subunit EBV-induced gene 3 or the IL-27 receptor WSX1 in the host animals had no effect on tumor growth inhibition induced by WSX1 expression in tumor cells. Expression of WSX1 in epithelial tumor cells enhances NK cell cytolytic activity against tumor cells, whereas the absence of functional NK cells impairs the WSX1-mediated inhibition of epithelial tumor growth. The underlying mechanism by which WSX1 expression in tumor cells enhances NK cytolytic activity is dependent on up-regulation of NKG2D ligand expression. Our results reveal an IL-27–independent function of WSX1: sensitizing NK cell-mediated antitumor surveillance via a NKG2D-dependent mechanism. [Cancer Res 2009;69(13):5505–13]