title: 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.affiliation: Deptartment of Internal Medicine, University of Turin, Italy. lina.matera@unito.it
authors.forename: Lina
authors.initials: L
authors.lastname: Matera
authors.forename: Sarah
authors.initials: S
authors.lastname: Forno
authors.forename: Alessandra
authors.initials: A
authors.lastname: Galetto
authors.forename: Francesco
authors.initials: F
authors.lastname: Moro
authors.forename: Stefano
authors.initials: S
authors.lastname: Garetto
authors.forename: Antonio
authors.initials: A
authors.lastname: Mussa
mesh_terms: D000951:Antigens, Neoplasm / Q000276:immunology; D002457:Cell Extracts; D003110:Colonic Neoplasms / Q000276:immunology*; D045142:Cross-Priming / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D005753:Gastric Mucosa / Q000276:immunology; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
chemical_list: D000951:Antigens, Neoplasm; D002457:Cell Extracts; D018840:HSP70 Heat-Shock Proteins; D015395:Histocompatibility Antigens Class I; D007371:Interferon-gamma