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Dendritic cell surface calreticulin is a receptor for NY-ESO-1: direct interactions between tumor-associated antigen

Gang Zeng1, Michael E Aldridge, Xiaoli Tian

  • 1Department of Urology, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA. gzeng@mednet.ucla.edu

Journal of Immunology (Baltimore, Md. : 1950)
|September 5, 2006
PubMed

Insights

The immune system

Area of Science:

  • Immunology
  • Cancer Immunology
  • Molecular Biology

Background:

  • The mechanisms by which the immune system recognizes endogenous tumors and mounts adaptive responses against nonmutated tumor-associated antigens (TAAs) are not fully understood.
  • Identifying intrinsic factors that influence TAA immunogenicity is crucial for developing effective cancer immunotherapies.

Purpose of the Study:

  • To investigate the intrinsic factors contributing to the immunogenicity of the tumor-associated antigen NY-ESO-1.
  • To identify the specific receptor on immune cells responsible for binding NY-ESO-1.

Main Methods:

  • NY-ESO-1 binding assays on various immune cell types.
  • Immunoprecipitation coupled with tandem mass spectrometry to identify NY-ESO-1 interacting proteins.
  • Blocking antibody experiments to assess the functional role of the identified receptor.

Main Results:

  • NY-ESO-1 protein was found to bind to the surface of immature dendritic cells (DCs), macrophages, and monocytes, but not B cells or T cells.
  • DC surface calreticulin was identified as the specific receptor for NY-ESO-1.
  • Calreticulin antibodies blocked NY-ESO-1 binding to immature DCs and its subsequent cross-presentation to CD8+ T cells in vitro.

Conclusions:

  • The interaction between NY-ESO-1 and calreticulin on immature dendritic cells provides a direct link between the tumor antigen and the innate immune system.
  • This interaction potentially bridges innate immune recognition with the initiation of adaptive immune responses against NY-ESO-1 expressing tumors.

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