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

Hanping Feng, Yi - Zeng, Michael W. Graner, Anna Likhacheva, Emmanuel Katsanis

Research output: Contribution to journalArticle

88 Citations (Scopus)

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 TH1 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.

Original languageEnglish (US)
Pages (from-to)245-252
Number of pages8
JournalBlood
Volume101
Issue number1
DOIs
StatePublished - Jan 1 2003

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Heat-Shock Proteins
Tumors
Immunity
Cells
T-cells
Neoplasms
Tissue
HSP70 Heat-Shock Proteins
Vaccination
Cell membranes
Liver
T-Lymphocytes
Severe Combined Immunodeficiency
Cytotoxic T-Lymphocytes
Apoptosis
Cytokines
Plasma Cells
Dendritic Cells
Hot Temperature
Cell Membrane

ASJC Scopus subject areas

  • Hematology

Cite this

Exogenous stress proteins enhance the immunogenicity of apoptotic tumor cells and stimulate antitumor immunity. / Feng, Hanping; Zeng, Yi -; Graner, Michael W.; Likhacheva, Anna; Katsanis, Emmanuel.

In: Blood, Vol. 101, No. 1, 01.01.2003, p. 245-252.

Research output: Contribution to journalArticle

Feng, Hanping ; Zeng, Yi - ; Graner, Michael W. ; Likhacheva, Anna ; Katsanis, Emmanuel. / Exogenous stress proteins enhance the immunogenicity of apoptotic tumor cells and stimulate antitumor immunity. In: Blood. 2003 ; Vol. 101, No. 1. pp. 245-252.
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