TY - JOUR
T1 - Induction of hsp70-mediated Th17 autoimmunity can be exploited as immunotherapy for metastatic prostate cancer
AU - Kottke, Timothy
AU - Sanchez-Perez, Luis
AU - Diaz, Rosa Maria
AU - Thompson, Jill
AU - Chong, Heung
AU - Harrington, Kevin
AU - Calderwood, Stuart K.
AU - Pulido, Jose
AU - Georgopoulos, Nick
AU - Selby, Peter
AU - Melcher, Alan
AU - Vile, Richard
PY - 2007/12/15
Y1 - 2007/12/15
N2 - 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.
AB - 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.
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U2 - 10.1158/0008-5472.CAN-07-2259
DO - 10.1158/0008-5472.CAN-07-2259
M3 - Article
C2 - 18089828
AN - SCOPUS:37549008775
SN - 0008-5472
VL - 67
SP - 11970
EP - 11979
JO - Cancer research
JF - Cancer research
IS - 24
ER -