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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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Blood, 1 January 2003, Vol. 101, No. 1, pp. 245-252
IMMUNOBIOLOGY
Exogenous stress proteins enhance the immunogenicity of apoptotic
tumor cells and stimulate antitumor immunity
Hanping Feng,
Yi Zeng,
Michael W. Graner,
Anna Likhacheva, and
Emmanuel Katsanis
From the Department of Pediatrics, Steele Memorial
Children's Research Center, University of Arizona, Tucson.
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

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