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

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.

CiteULike Connotea Del.icio.us Digg Reddit Technorati What's this?
This article has been cited by other articles:

|
 |

|
 |
 
N. Larmonier, J. Cantrell, C. LaCasse, G. Li, N. Janikashvili, E. Situ, M. Sepassi, S. Andreansky, and E. Katsanis
Chaperone-rich tumor cell lysate-mediated activation of antigen-presenting cells resists regulatory T cell suppression
J. Leukoc. Biol.,
April 1, 2008;
83(4):
1049 - 1059.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
K. L. Kislin, M. T. Marron, G. Li, M. W. Graner, and E. Katsanis
Chaperone-rich cell lysate embedded with BCR-ABL peptide demonstrates enhanced anti-tumor activity against a murine BCR-ABL positive leukemia
FASEB J,
July 1, 2007;
21(9):
2173 - 2184.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
N. C. Di Paolo, S. Tuve, S. Ni, K. E. Hellstrom, I. Hellstrom, and A. Lieber
Effect of Adenovirus-Mediated Heat Shock Protein Expression and Oncolysis in Combination with Low-Dose Cyclophosphamide Treatment on Antitumor Immune Responses
Cancer Res.,
January 15, 2006;
66(2):
960 - 969.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
C. Massa, C. Melani, and M. P. Colombo
Chaperon and Adjuvant Activity of hsp70: Different Natural Killer Requirement for Cross-Priming of Chaperoned and Bystander Antigens
Cancer Res.,
September 1, 2005;
65(17):
7942 - 7949.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. Clayton, A. Turkes, H. Navabi, M. D. Mason, and Z. Tabi
Induction of heat shock proteins in B-cell exosomes
J. Cell Sci.,
August 15, 2005;
118(16):
3631 - 3638.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. W. Graner and D. D. Bigner
Chaperone proteins and brain tumors: Potential targets and possible therapeutics
Neuro-oncol,
July 1, 2005;
7(3):
260 - 278.
[Abstract]
[PDF]
|
 |
|

|
 |

|
 |
 
H. Feng, D. Zhang, D. Palliser, P. Zhu, S. Cai, A. Schlesinger, L. Maliszewski, and J. Lieberman
Listeria-Infected Myeloid Dendritic Cells Produce IFN-{beta}, Priming T Cell Activation
J. Immunol.,
July 1, 2005;
175(1):
421 - 432.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
G. I. Lancaster and M. A. Febbraio
Exosome-dependent Trafficking of HSP70: A NOVEL SECRETORY PATHWAY FOR CELLULAR STRESS PROTEINS
J. Biol. Chem.,
June 17, 2005;
280(24):
23349 - 23355.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
Y. Zeng, M. W. Graner, S. Thompson, M. Marron, and E. Katsanis
Induction of BCR-ABL-specific immunity following vaccination with chaperone-rich cell lysates derived from BCR-ABL+ tumor cells
Blood,
March 1, 2005;
105(5):
2016 - 2022.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
L. Zheng, M. He, M. Long, R. Blomgran, and O. Stendahl
Pathogen-Induced Apoptotic Neutrophils Express Heat Shock Proteins and Elicit Activation of Human Macrophages
J. Immunol.,
November 15, 2004;
173(10):
6319 - 6326.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
Y. Zeng, H. Feng, M. W. Graner, and E. Katsanis
Tumor-derived, chaperone-rich cell lysate activates dendritic cells and elicits potent antitumor immunity
Blood,
June 1, 2003;
101(11):
4485 - 4491.
[Abstract]
[Full Text]
[PDF]
|
 |
|
|
|