Exogenous stress proteins enhance the immunogenicity of apoptotic tumor cells and stimulate antitumor immunity.
We have previously reported that apoptotic tumor cells can be either immunogenic or nonimmunogenic in vivo, depending on whether or not these cells are heat stressed before induction of apoptosis. Stressed apoptotic cells express heat shock proteins on their plasma membranes and dendritic cells are capable of distinguishing them from nonstressed apoptotic cells. Here we provide evidence that when purified heat shock protein 70 or chaperone-rich cell lysate (CRCL) from syngeneic normal tissue is used as an adjuvant with nonimmunogenic apoptotic tumor cells in vaccination, potent antitumor immunity can be generated. This antitumor immunity is mediated by T cells because antitumor effects are not observed in either severe combined immunodeficiency or T cell-depleted mice. We further demonstrate that vaccination of mice with apoptotic tumor cells mixed with liver-derived CRCL as adjuvant were capable of enhancing the production of T(H)1 cytokines, inducing specific cytotoxic T lymphocytes and eliciting long-lasting antitumor immunity. Stress proteins from autologous normal tissue components therefore can serve as danger signals to enhance the immunogenicity of apoptotic tumor cells and stimulate tumor-specific immunity
Feng
Hanping
H
Department of Pediatrics, Steele Memorial Children's Research Center, University of Arizona, Tucson 85724, USA.
Zeng
Yi
Y
Graner
Michael W
MW
Likhacheva
Anna
A
Katsanis
Emmanuel
E
D000276:Adjuvants, Immunologic / Q000627:therapeutic use; D000818:Animals; D017209:Apoptosis; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000276:immunology; D016207:Cytokines / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D005260:Female; D018840:HSP70 Heat-Shock Proteins / Q000276:immunology / Q000627:therapeutic use; D006360:Heat-Shock Proteins / Q000276:immunology / Q000494:pharmacology* / Q000627:therapeutic use; D007109:Immunity / Q000187:drug effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D018832:Molecular Chaperones / Q000276:immunology / Q000627:therapeutic use; D009369:Neoplasms / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology
D000276:Adjuvants, Immunologic; D019496:Cancer Vaccines; D016207:Cytokines; D018840:HSP70 Heat-Shock Proteins; D006360:Heat-Shock Proteins; C490434:Hspa2 protein, mouse; D018832:Molecular Chaperones