Tumor-produced secreted form of binding of immunoglobulin protein elicits antigen-specific tumor immunity.

Abstract

Binding of immunoglobulin protein (BiP) is a major molecular chaperone localized in endoplasmic reticulum (ER). It has been demonstrated to interact with nascent Ig. However, contrary to other ER-resident heat shock proteins such as gp96, calreticulin, and ORP150, it is not clear whether tumor-derived BiP plays a role in inducing antitumor immunity. In this study, we show that the tumor-derived secreted form of BiP is capable of inducing antitumor CD8(+) T cell responses. We constructed an ER-retention signal KDEL-deleted mutant of BiP cDNA and transfected it to tumor cells, which resulted in continuous secretion of tumor-derived BiP into the extracellular milieu. We show that this secreted BiP is taken up by bone marrow-derived dendritic cells, and thereafter BiP-associated Ag peptide is cross-presented in association with MHC class I molecules, resulting in elicitation of an Ag-specific CD8(+) T cell response and antitumor effect. This strategy to boost antitumor immune responses shows that a tumor could be its own cellular vaccine via gene modification of the secretion of the tumor Ag-BiP complex.

• Authors: Yasuaki Tamura, Yoshihiko Hirohashi, Goro Kutomi, Katsuya Nakanishi, Kenjirou Kamiguchi, Toshihiko Torigoe, Noriyuki Sato
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 186 Issue 7 Pg. 4325-30 (Apr 01 2011) ISSN: 1550-6606 [Electronic] United States
• PMID: 21339366 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, Neoplasm
• Endoplasmic Reticulum Chaperone BiP
• Epitopes
• Heat-Shock Proteins

Topics

• Amino Acid Sequence
• Animals
• Antigens, Neoplasm (genetics, immunology)
• Binding Sites, Antibody (genetics, immunology)
• Cell Line, Tumor
• Cells, Cultured
• Colonic Neoplasms (immunology, metabolism)
• Cross-Priming (genetics, immunology)
• Endoplasmic Reticulum Chaperone BiP
• Epitopes (genetics, immunology)
• Female
• Heat-Shock Proteins (genetics, metabolism)
• Lung Neoplasms (immunology, metabolism)
• Mice
• Mice, Inbred BALB C
• Mice, Inbred C3H
• Mice, Inbred C57BL
• Mice, Nude
• Molecular Sequence Data
• Thymoma (immunology, metabolism)