Spontaneous immunity against Bcl-X-L in cancer patients

Mads Hald Andersen, Sine Reker Hadrup, Pia Kvistborg, Jürgen C. Becker, Per thor Straten

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

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-1derived peptides in patients suffering from cancers of different origin. In this study, we demonstrate that Bcl-XL 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-XL 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.
Original languageEnglish
JournalJournal of Immunology
Volume175
Issue number4
Pages (from-to)2709-2714
Number of pages6
ISSN0022-1767
DOIs
Publication statusPublished - 2005
Externally publishedYes

Keywords

  • Immunology
  • gamma interferon
  • granzyme B
  • HLA A2 antigen
  • major histocompatibility antigen
  • protein bcl 2
  • protein bcl xl
  • protein mcl 1
  • apoptosis
  • article
  • breast cancer
  • cancer immunotherapy
  • cell survival
  • cellular immunity
  • controlled study
  • cytotoxic T lymphocyte
  • enzyme linked immunospot assay
  • flow cytometry
  • gene expression regulation
  • gene overexpression
  • human
  • human cell
  • melanoma
  • metastasis
  • pancreas cancer
  • peripheral lymphocyte
  • priority journal
  • tumor growth
  • tumor immunity
  • bcl-X Protein
  • Breast Neoplasms
  • Cell Line
  • Cell Line, Tumor
  • Cytotoxicity Tests, Immunologic
  • Enzyme-Linked Immunosorbent Assay
  • Epitopes, T-Lymphocyte
  • Female
  • Flow Cytometry
  • Granzymes
  • HLA-A2 Antigen
  • Humans
  • Immunity, Cellular
  • Immunity, Natural
  • Leukocytes, Mononuclear
  • Melanoma
  • Neoplasm Proteins
  • Peptide Fragments
  • Protein Binding
  • Serine Endopeptidases
  • T-Lymphocytes, Cytotoxic
  • Immunity, Innate
  • EC 3.4.21.- GZMB protein, human
  • EC 3.4.21.- Granzymes
  • EC 3.4.21.- Serine Endopeptidases
  • IMMUNOLOGY
  • T-CELL RESPONSES
  • I MHC MOLECULES
  • ELISPOT ASSAY
  • MELANOMA
  • PEPTIDES
  • IDENTIFICATION
  • PROTEIN
  • CHEMORESISTANCE
  • LYMPHOCYTES
  • VACCINATION
  • Primates Mammalia Vertebrata Chordata Animalia (Animals, Chordates, Humans, Mammals, Primates, Vertebrates) - Hominidae [86215] human common
  • human bcl-x gene [Hominidae]
  • antiapoptotic protein
  • Bcl-2
  • Bcl-X-L
  • CTL
  • HLA-A2
  • Mcl-1
  • MHC molecule
  • peptide epitope
  • tumor-associated Ags
  • 02506, Cytology - Animal
  • 02508, Cytology - Human
  • 03502, Genetics - General
  • 03508, Genetics - Human
  • 10064, Biochemistry studies - Proteins, peptides and amino acids
  • 15002, Blood - Blood and lymph studies
  • 15004, Blood - Blood cell studies
  • 24003, Neoplasms - Immunology
  • 24004, Neoplasms - Pathology, clinical aspects and systemic effects
  • 34502, Immunology - General and methods
  • 34508, Immunology - Immunopathology, tissue immunology
  • Immune System
  • Molecular Genetics
  • Tumor Biology
  • drug resistance
  • spontaneous immunity
  • tumor progression
  • cancer Neoplasms (MeSH) neoplastic disease
  • Biochemistry and Molecular Biophysics
  • Chemical Coordination and Homeostasis
  • T cell immune system, blood and lymphatics
  • immunotherapy laboratory techniques, immunologic techniques, clinical techniques, therapeutic and prophylactic techniques

Cite this

Andersen, M. H., Hadrup, S. R., Kvistborg, P., Becker, J. C., & Straten, P. T. (2005). Spontaneous immunity against Bcl-X-L in cancer patients. Journal of Immunology, 175(4), 2709-2714. https://doi.org/10.4049/jimmunol.175.4.2709