Increased expression of HSP70 by colon cancer cells is not always associated with access to the dendritic cell cross-presentation pathway.

Abstract

Dendritic cells (DCs) are highly specialized antigen-presenting cells endowed with the unique ability to not only present exogenous antigens upon exposure to MHC II, but also to cross-present these upon exposure to MHC I. This property was exploited to generate the tumor-specific CD8 cytotoxic lymphocyte (CTL) response in DCs-based cancer vaccine protocols. In this context, the source of tumor antigens remains a critical challenge. A crude tumor in the context of danger signals is believed to represent an efficient source of tumor antigens (TAs) for DCs loading. In our previous work, increased DCs cross-presentation of antigens from necrotic gastric carcinoma cells paralleled up-regulation of the heat shock protein hsp70. We studied the expression of hsp70 on primary colon carcinoma cells and its relevance in the cross-priming of anti-tumor CTL by tumor-loaded DCs. Hsp70 was expressed on all three of the tumors studied, but was never detected in the peritumoral normal mucosa (NM). The uptake of the tumor induced a trend towards down-modulation of the monocyte-specific marker CD14, but had no effect on the chemokine receptors CCR4 and CCR7. The IFN-gamma enzyme-linked immunospot assay (ELIspot) showed cross-priming of CTL by tumor-loaded but not NM-loaded DCs in four of the six cases studied. The CTL response generated in DC+tumor cultures was directed towards the tumor, but not towards NM, and it was characterized by refractoriness to polyclonal (Ca ionophores, PKC activators) stimuli. Of the three CTL-generating tumors, only one expressed hsp70. This data indicates a tumor-specific expression of hsp70, but does not support its relevance in the DC cross-presentation of TAs.

• Authors: Lina Matera, Sarah Forno, Alessandra Galetto, Francesco Moro, Stefano Garetto, Antonio Mussa
• Journal: Cellular & molecular biology letters (Cell Mol Biol Lett) Vol. 12 Issue 2 Pg. 268-79 ( 2007) ISSN: 1689-1392 [Electronic] England
• PMID: 17235439 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, Neoplasm
• Cell Extracts
• HSP70 Heat-Shock Proteins
• Histocompatibility Antigens Class I
• Interferon-gamma

Topics

• Antigens, Neoplasm (immunology)
• Cell Extracts
• Colonic Neoplasms (immunology)
• Cross-Priming (immunology)
• Dendritic Cells (immunology)
• Gastric Mucosa (immunology)
• HSP70 Heat-Shock Proteins (metabolism)
• Histocompatibility Antigens Class I (immunology)
• Humans
• Interferon-gamma (immunology)
• T-Lymphocytes, Cytotoxic (immunology)