Stressed apoptotic tumor cells express heat shock proteins and elicit tumor-specific immunity

Hanping Feng, Yi Zeng, Luke Whitesell, Emmanuel Katsanis

Research output: Contribution to journalArticle

130 Scopus citations

Abstract

In attempting to develop effective anticancer immunotherapies, the relative ability of apoptotic cells to induce an immune response remains an important but controversial consideration. A novel genetransfer approach was used by which rapid induction of pure apoptosis can be selectively achieved in a transfected tumor cell population following exposure to a semisynthetic dimerizing ligand, AP20187. Inoculation of BALB/c mice with apoptotic and viable 12B1-D1 leukemia cells, at a 12:1 ratio subcutaneously, led to early tumor growth. Heat stress up-regulated the expression of membrane heat shock proteins (HSP72 and HSP60) on apoptotic 12B1-D1 cells, and stressed apoptotic cells were capable of generating a T-cell-mediated specific antitumor response. Pulsing of stressed apoptotic leukemia cells onto syngeneic dendritic cells resulted largely in rejection of coinjected viable 1281-D1 cells. Mice rejecting the primary 12B1-D1 inoculum were immune to the same but not to a different leukemia challenge. Our findings indicate that tumor immunogenicity is dependent on whether cells are stressed before apoptosis induction and suggest that the immune system is capable of distinguishing between stressed and nonstressed cells undergoing programmed cell death.

Original languageEnglish (US)
Pages (from-to)3505-3512
Number of pages8
JournalBlood
Volume97
Issue number11
DOIs
StatePublished - Jun 1 2001

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Fingerprint Dive into the research topics of 'Stressed apoptotic tumor cells express heat shock proteins and elicit tumor-specific immunity'. Together they form a unique fingerprint.

  • Cite this