Induction of cell stress through gene transfer of an engineered heat shock transcription factor enhances tumor immunogenicity.
Heat shock protein expression and release is closely associated with immunogenic forms of cell death. We show that activation of the stress response within tumor cells during cell death, using an engineered form of the heat shock transcription factor, leads to an immunogenic death. Cells dying through 'stressful death' show decreased phagocytosis by macrophages in vitro. Moreover, cells expressing heat shock proteins during cell death are significantly more protective against subsequent tumor challenge. These data demonstrate the utility of activating cellular stress programs over the course of cytotoxic therapies to enhance immune responses to dying cells.
Gough
M J
MJ
Molecular Medicine Program, Mayo Clinic, Rochester, MN, USA.
Melcher
A A
AA
Crittenden
M R
MR
Sanchez-Perez
L
L
Voellmy
R
R
Vile
R G
RG
D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use; D017209:Apoptosis / Q000276:immunology; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000276:immunology / Q000378:metabolism / Q000628:therapy*; D004268:DNA-Binding Proteins / Q000235:genetics*; D005434:Flow Cytometry; D015774:Ganciclovir / Q000627:therapeutic use; D015870:Gene Expression; D005786:Gene Expression Regulation; D015316:Genetic Therapy / Q000379:methods*; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D000076249:Heat Shock Transcription Factors; D017737:Macrophages, Peritoneal / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D010587:Phagocytosis; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D018139:Simplexvirus / Q000235:genetics; D019311:Staurosporine / Q000627:therapeutic use; D013937:Thymidine Kinase / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors
D000998:Antiviral Agents; D004268:DNA-Binding Proteins; D018840:HSP70 Heat-Shock Proteins; D000076249:Heat Shock Transcription Factors; D014157:Transcription Factors; D013937:Thymidine Kinase; D011493:Protein Kinase C; D019311:Staurosporine; D015774:Ganciclovir