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 Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Andersen, M. H. Articles by Straten, P. t. Search for Related Content PubMed PubMed Citation Articles by Andersen, M. H. Articles by Straten, P. t.

Spontaneous Immunity against Bcl-x_L in Cancer Patients ¹

Mads Hald Andersen^2,*, Sine Reker^*, Pia Kvistborg^*, Jürgen C. Becker and Per thor Straten^*

^* Tumor Immunology Group, Institute of Cancer Biology, Danish Cancer Society, Copenhagen, Denmark; and Department of Dermatology, University of Würzburg, Würzburg, Germany

It is well-established that peptide epitopes derived from human tumor-associated Ags can be recognized by CTL in the context of the MHC molecule. However, the vast majority of Ags described are not vital for survival and growth of the tumor cells, and immunoselection of Ag-loss variants during immunotherapy has been demonstrated in several cases. Malfunctions in death pathways observed in human cancers are often due to overexpression of antiapoptotic proteins in the Bcl-2 protein family, i.e., Bcl-2, Mcl-1, and Bcl-x_L. These antiapoptotic proteins are implicated in cancer development, tumor progression, and drug resistance. The general overexpression of the antiapoptotic members of the Bcl-2 family in cancer and the fact that down-regulation or loss of expression of these proteins as a means of immune escape would impair sustained tumor growth makes them very attractive targets for anticancer immunotherapy. Recently, we identified spontaneous T cell responses against Bcl-2- and Mcl-1-derived peptides in patients suffering from cancers of different origin. In this study, we demonstrate that Bcl-x_L is a target for T cell recognition in cancer patients. Thus, we describe spontaneous HLA-A2-restricted cytotoxic T cell responses against peptide epitopes derived from Bcl-x_L by means of ELISPOT and flow cytometry stainings, whereas no responses were detected against any of the Bcl-x_L epitopes in any healthy controls. Moreover, Bcl-x_L-specific T cells are cytotoxic against HLA-matched cancer cells of different origin. Thus, cellular immune responses against apoptosis inhibitors like the Bcl-2 family proteins appear to represent a general feature in cancer.

This article has been cited by other articles:

				Y. Dang, K. L. Knutson, V. Goodell, C. dela Rosa, L. G. Salazar, D. Higgins, J. Childs, and M. L. Disis Tumor Antigen-Specific T-Cell Expansion Is Greatly Facilitated by In vivo Priming Clin. Cancer Res., March 15, 2007; 13(6): 1883 - 1891. [Abstract] [Full Text] [PDF]