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

• Published in: Cellular & molecular biology letters 2007-04, Vol.12 (2), p.268-279
• Main Authors: Matera, Lina, Forno, Sarah, Galetto, Alessandra, Moro, Francesco, Garetto, Stefano, Mussa, Antonio
• Format: Article
• Language: English
• Subjects: Antigens, Neoplasm - immunology; Cell Extracts; Colon cancer; Colonic Neoplasms - immunology; Colorectal cancer; Cross-Priming - immunology; Cytotoxic T lymphocyte; Dendritic cells; Dendritic Cells - immunology; Gastric Mucosa - immunology; Heat shock proteins; Histocompatibility Antigens Class I - immunology; HSP70 Heat-Shock Proteins - metabolism; Humans; Interferon-gamma - immunology; Necrosis; T-Lymphocytes, Cytotoxic - immunology
• ISSN: 1689-1392; 1425-8153; 1689-1392
• DOI: 10.2478/s11658-007-0001-6

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-γ 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.