Induction of hsp70-mediated Th17 autoimmunity can be exploited as immunotherapy for metastatic prostate cancer.
A close connectivity between autoimmune and tumor rejection responses is known to exist in the case of melanoma immunotherapy. However, relatively little is known about self-antigens on other types of normal cells, their relation to the development of autoimmune disease, and their possible coexistence as potential tumor rejection antigens on associated tumors. In the current study, we induced inflammatory killing of normal prostate tissue in situ using a fusogenic membrane glycoprotein along with the immune adjuvant hsp70. We show here that, in the prostate, hsp70 induces interleukin (IL)-6, which triggers a CD4- and CD8-dependent progressive autoimmune reactivity, associated with IL-17 expression. This autoimmune response was also able to induce the rejection of established prostate tumors, but not other histologic types of tumors, growing elsewhere in the animal. These data show that the intimate connectivity between autoimmune and tumor rejection responses extends beyond the classic melanoma paradigm and may be clinically valuable for the treatment of established metastatic disease of the prostate.
Kottke
Timothy
T
Molecular Medicine Program, Mayo Clinic, Rochester, Minnesota 55902, USA.
Sanchez-Perez
Luis
L
Diaz
Rosa Maria
RM
Thompson
Jill
J
Chong
Heung
H
Harrington
Kevin
K
Calderwood
Stuart K
SK
Pulido
Jose
J
Georgopoulos
Nick
N
Selby
Peter
P
Melcher
Alan
A
Vile
Richard
R
D000818:Animals; D015551:Autoimmunity; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D018840:HSP70 Heat-Shock Proteins / Q000502:physiology* / Q000627:therapeutic use*; D007167:Immunotherapy / Q000379:methods*; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D020381:Interleukin-17 / Q000627:therapeutic use*; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000378:metabolism; D008198:Lymph Nodes / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009362:Neoplasm Metastasis; D011471:Prostatic Neoplasms / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D013601:T-Lymphocytes / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology*
D018840:HSP70 Heat-Shock Proteins; D020381:Interleukin-17; D015850:Interleukin-6