PMID- 17235439 OWN - NLM STAT- MEDLINE DCOM- 20070823 LR - 20181217 IS - 1689-1392 (Electronic) IS - 1425-8153 (Print) IS - 1425-8153 (Linking) VI - 12 IP - 2 DP - 2007 TI - Increased expression of HSP70 by colon cancer cells is not always associated with access to the dendritic cell cross-presentation pathway. PG - 268-79 AB - 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. FAU - Matera, Lina AU - Matera L AD - Deptartment of Internal Medicine, University of Turin, Italy. lina.matera@unito.it FAU - Forno, Sarah AU - Forno S FAU - Galetto, Alessandra AU - Galetto A FAU - Moro, Francesco AU - Moro F FAU - Garetto, Stefano AU - Garetto S FAU - Mussa, Antonio AU - Mussa A LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20070119 PL - England TA - Cell Mol Biol Lett JT - Cellular & molecular biology letters JID - 9607427 RN - 0 (Antigens, Neoplasm) RN - 0 (Cell Extracts) RN - 0 (HSP70 Heat-Shock Proteins) RN - 0 (Histocompatibility Antigens Class I) RN - 82115-62-6 (Interferon-gamma) SB - IM MH - Antigens, Neoplasm/immunology MH - Cell Extracts MH - Colonic Neoplasms/*immunology MH - Cross-Priming/*immunology MH - Dendritic Cells/*immunology MH - Gastric Mucosa/immunology MH - HSP70 Heat-Shock Proteins/*metabolism MH - Histocompatibility Antigens Class I/immunology MH - Humans MH - Interferon-gamma/immunology MH - T-Lymphocytes, Cytotoxic/immunology PMC - PMC6275593 EDAT- 2007/01/20 09:00 MHDA- 2007/08/24 09:00 PMCR- 2007/01/19 CRDT- 2007/01/20 09:00 PHST- 2006/08/01 00:00 [received] PHST- 2006/10/23 00:00 [accepted] PHST- 2007/01/20 09:00 [pubmed] PHST- 2007/08/24 09:00 [medline] PHST- 2007/01/20 09:00 [entrez] PHST- 2007/01/19 00:00 [pmc-release] AID - 1 [pii] AID - 10.2478/s11658-007-0001-6 [doi] PST - ppublish SO - Cell Mol Biol Lett. 2007;12(2):268-79. doi: 10.2478/s11658-007-0001-6. Epub 2007 Jan 19.