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Prepublished online as a Blood First Edition Paper on August 22, 2002; DOI 10.1182/blood-2002-05-1580.

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2002-05-1580v1
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Submitted May 29, 2002
Accepted August 7, 2002

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

Hanping Feng, Yi Zeng, Michael W Graner, Anna Likhacheva, and Emmanuel Katsanis*

Department of Pediatrics, University of Arizona, Tucson, AZ, USA

* Corresponding author; email: katsanis{at}peds.arizona.edu.

We have previously reported that apoptotic tumor cells can be either immunogenic or non-immunogenic in vivo, depending upon whether or not these cells are heat stressed before apoptosis induction. Stressed apoptotic cells express heat shock proteins on their plasma membranes, and dendritic cells, are capable of distinguishing them from non-stressed apoptotic cells. Here we provide evidence that when purified heat shock protein 70 or chaperone-rich cell lysate (CRCL) from syngeneic normal tissue are used as adjuvants with non-immunogenic apoptotic tumor cells in vaccination, potent anti-tumor immunity can be generated. This anti-tumor immunity is T-cell mediated, since anti-tumor 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 anti-tumor 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.


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