HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Related articles in The JI Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Chen, P. W. Articles by Ksander, B. R. Search for Related Content PubMed PubMed Citation Articles by Chen, P. W. Articles by Ksander, B. R.

Tumor Escape Mutants Develop within an Immune-Privileged Environment in the Absence of T Cell Selection

Peter W. Chen^*, Toshihiko Uno and Bruce R. Ksander^1,,

^* Department of Ophthalmology, University of Texas Southwestern Medical Center, Dallas, TX 75390; Ehime University School of Medicine, Ehime, Japan; Schepens Eye Research Institute, Boston, MA 02114; and Department of Ophthalmology, Harvard Medical School, Boston, MA 02114

The establishment of tumor escape mutants, which can be driven by innate and/or adaptive immune effector cells, presents a significant obstacle in the development of successful tumor immunotherapies. Our study documents that tumors growing within an immune-privileged site within the eye develop a tumor escape phenotype in the absence of selective T cell pressure. P815 tumor cells that are recovered from progressively growing tumors within the anterior chamber of the eye escape elimination when injected into the flanks of a second group of syngeneic DBA/2 mice that were previously immunized against P815 tumor cells. The escape phenotype of eye-derived P815 tumors was stable and permanent when the tumor cells were cultured in vitro. Eye-derived tumor cells recovered from the anterior chamber of CB-17 SCID mice also escaped elimination when injected into the flanks of immunized mice, demonstrating that selective pressure by tumor Ag-specific T cells did not contribute to the development of the escape phenotype. In vitro studies demonstrated that eye-derived tumor cells were not lysed by specific CTL and were unable to restimulate primed Ag-specific T cells. Immune escape of eye-derived tumor cells was not due to down-regulation of either MHC class I or ICAM-1. Our data demonstrate that the immune-privileged environment within the eye induces a tumor escape phenotype that is not driven by selective T cell pressure. We predict that immune escape within the eye is driven by the unique ocular environment that permanently alters gene expression in eye-derived tumor cells.

Related articles in The JI:

IN THIS ISSUE

The JI 2006 177: 1-2. [Full Text]  

This article has been cited by other articles:

				O. Goldberger, I. Volovitz, A. Machlenkin, E. Vadai, E. Tzehoval, and L. Eisenbach Exuberated Numbers of Tumor-Specific T Cells Result in Tumor Escape Cancer Res., May 1, 2008; 68(9): 3450 - 3457. [Abstract] [Full Text] [PDF]