EpCAM is an Important Suppressor of Anti-Tumor Immunity

Abstract

To the editor: Nechansky and Kircheis appropriately note that, following the publication our review in Cancer Biology and Therapy, the manuscript reporting that EpCAM was the ligand for LAIR-1 was retracted due to technical errors in the experimental design(1). We cited the LAIR-1/EpCAM hypothesis as a possible mechanism by which EpCAM expressing tumors might evade host immune responses. Our more recent work2 supports such a functional role for EpCAM in an immunosuppressive role, albeit not involving LAIR-1. In this more recent publication we demonstrate that EpCAM (GA733-2) expression inhibits antigen presentation by human dendritic cells and note that it is yet to be determined whether the effect is due to interference with MHC class II/peptide-TCR interactions or as a result of interference with other cell surface interactions between antigen presenting cells (dendritic cells) and CD4+ T cells. Although not published, Dr. Meyaard was kind enough to provide us with her reagents and we were not able to confirm a role for LAIR-1 in the inhibitory effect of EpCAM in the assays we used. Nonetheless, the inhibitory effects of EpCAM and its murine homologue mouse epithelial glycoprotein (mEGP) are quite profound. Expression of these proteins in dendritic cells abrogates responses from antigen-specific and alloreactive CD4+ T cells and dendritic cells exposed to cell debris from tumors expressing these proteins are likewise unable to stimulate T cell responses. This is also borne out by in vivo testing of the murine antigen. Thus, a variety of murine (in vitro and in vivo) and human (in vitro) experiments all substantiate the role of the EpCAM in immune suppression(2).Stephen L. Eck, Pfizer Global Research & Development, Ann Arbor, MI 48105Andrew Armstrong, Johns Hopkins University, Baltimore, MD 212311. Meyaard L. van der Vuurst de Vries AR. de Ruiter T. Lanier LL. Phillips JH. Clevers H. The epithelial cellular adhesion molecule (Ep-CAM) is a ligand for the leukocyte-associated immunoglobulin-like receptor (LAIR). 194(1):107-12, 2001 Jul 2. Retraction in Meyaard L, van der Vuurst de Vries AR, de Ruiter T, Lanier LL, Phillips JH, Clevers H. J Exp Med. 2003 Oct 6;198(7):1129; 2. Gutzmer R. Li W. Sutterwala S. Lemos MP. Elizalde JI. Urtishak SL. Behrens EM. Rivers PM. Schlienger K. Laufer TM. Eck SL. Marks MS. A tumor-associated glycoprotein that blocks MHC class II-dependent antigen presentation by dendritic cells. Journal of Immunology. 173(2):1023-32, 2004 Jul 15