This Article Full Text Full Text (PDF) Other Versions of this Article: JVI.01943-06v1 81/3/1313    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Lowe, D. B. Articles by Kennedy, R. C. Search for Related Content PubMed PubMed Citation Articles by Lowe, D. B. Articles by Kennedy, R. C.

 Previous Article  |  Next Article 

Journal of Virology, February 2007, p. 1313-1318, Vol. 81, No. 3
0022-538X/07/$08.00+0     doi:10.1128/JVI.01943-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Fc Receptors Play a Dominant Role in Protective Tumor Immunity against a Virus-Encoded Tumor-Specific Antigen in a Murine Model of Experimental Pulmonary Metastases

Departments of Microbiology and Immunology,¹ Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, Texas,² Southwest Cancer Treatment and Research Center, Lubbock, Texas³

Received 6 September 2006/ Accepted 5 November 2006

Simian virus 40 (SV40) large tumor antigen (Tag) represents a virus-encoded tumor-specific antigen expressed in many types of human cancers and a potential immunologic target for antitumor responses. Fc receptors are important mediators in the regulation and execution of host effector mechanisms against conditions including infectious diseases, autoimmunity, and cancer. By examining tumor protection in SV40 Tag-immunized wild-type BALB/c mice using an experimental pulmonary metastasis model, we attempted to address whether engagement of the immunoglobulin G Fc receptors (FcRs) on effector cells is necessary to mediate antitumor responses. All immunized BALB/c FcR^–/– knockout mice developed anti-SV40 Tag antibody responses prior to experimental challenge with a tumorigenic cell line expressing SV40 Tag. However, all mice deficient in the activating FcRI (CD64) and FcRIII (CD16) were unable to mount protective immunologic responses against tumor challenge and developed tumor lung foci. In contrast, mice lacking the inhibitory receptor FcRII (CD32) demonstrated resistance to tumorigenesis. These results underscore the importance of effector cell populations expressing FcRI/III within this murine tumor model system, and along with the production of a specific humoral immune response, antibody-dependent cell-mediated cytotoxicity (ADCC) may be a functioning mechanism of tumor clearance. Additionally, these data demonstrate the potential utility of ADCC as a viable approach for targeting vaccination strategies that promote FcRI/III scavenging pathways against cancer.

Published ahead of print on 15 November 2006.