Exogenous stress proteins enhance the immunogenicity of apoptotic tumor cells and stimulate antitumor immunity.

Abstract

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

• Authors: Hanping Feng, Yi Zeng, Michael W Graner, Anna Likhacheva, Emmanuel Katsanis
• Journal: Blood (Blood) Vol. 101 Issue 1 Pg. 245-52 (Jan 01 2003) ISSN: 0006-4971 [Print] United States
• PMID: 12393411 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adjuvants, Immunologic
• Cancer Vaccines
• Cytokines
• HSP70 Heat-Shock Proteins
• Heat-Shock Proteins
• Hspa2 protein, mouse
• Molecular Chaperones

Topics

• Adjuvants, Immunologic (therapeutic use)
• Animals
• Apoptosis
• Cancer Vaccines (administration & dosage, immunology)
• Cytokines (drug effects)
• Drug Evaluation, Preclinical
• Female
• HSP70 Heat-Shock Proteins (immunology, therapeutic use)
• Heat-Shock Proteins (immunology, pharmacology, therapeutic use)
• Immunity (drug effects)
• Mice
• Mice, Inbred BALB C
• Molecular Chaperones (immunology, therapeutic use)
• Neoplasms (immunology, pathology, therapy)
• T-Lymphocytes, Cytotoxic (drug effects, immunology)
• Th1 Cells (drug effects, immunology)