Response to sublethal heat treatment of prostatic tumor cells and of prostatic tumor infiltrating T-cells.
BACKGROUND
To investigate the possibilities offered by high intensity focused ultrasound (HIFU) in the field of tumor vaccination, we analyzed how prostatic cancer (CaP) cells react towards heat treatment and whether increased access to CaP cells by the immune system would be the result.


METHODS
Heat/stress response of CaP cells in situ and of CaP cell lines was analyzed by immunohistochemistry, Western blotting, and Atlas array. A heat-induced change in immune recognition was analyzed functionally using human T-helper (Th)1 and Th2-cytokine release with tumor infiltrating T-lymphocytes (TIL) as responder and autologous CaP cells either heated or untreated as stimulator cells.


RESULTS
Transcription of 68 out of 500 genes was upregulated by sublethal heat in LNCaP and PC3 cells. Significantly upregulated stress protein (SP) expression (HSP-72, -73, GRP-75, -78) was seen at the border zone of HIFU treatment. Remarkably, even untreated benign prostatic hyperplasia (BPH) specimens revealed relative overexpression of heat shock protein (HSP)-72, -73 and glucose regulated protein (GRP)-75, -78. Heated CaP cells increased Th1-cytokine (IL-2, IFN-gamma, TNF-alpha) release but decreased Th2-cytokine (IL-4, -5, -10) release of TIL.


CONCLUSIONS
HIFU treatment may alter the presentation of prostate tissue and tumor antigens and this presentation is most likely stimulatory. HSP-72/73 overexpression in untreated BPH may suggest a mechanism by which BPH can incite inflammation.
Kramer
Gero
G
Department of Urology, University of Vienna, Austria.
Steiner
Georg E
GE
Gröbl
Marion
M
Hrachowitz
Kristian
K
Reithmayr
Franz
F
Paucz
Ljubomir
L
Newman
Martin
M
Madersbacher
Stephan
S
Gruber
Diego
D
Susani
Martin
M
Marberger
Michael
M
D000951:Antigens, Neoplasm / Q000276:immunology*; D015153:Blotting, Western; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology*; D015972:Gene Expression Regulation, Neoplastic; D006360:Heat-Shock Proteins / Q000096:biosynthesis; D006358:Hot Temperature; D006801:Humans; D006979:Hyperthermia, Induced; D007150:Immunohistochemistry; D007249:Inflammation; D016246:Lymphocytes, Tumor-Infiltrating; D008297:Male; D011470:Prostatic Hyperplasia / Q000235:genetics / Q000473:pathology*; D011471:Prostatic Neoplasms / Q000235:genetics / Q000473:pathology*; D013601:T-Lymphocytes; D014407:Tumor Cells, Cultured; D014465:Ultrasonics; D015854:Up-Regulation
D000951:Antigens, Neoplasm; D016207:Cytokines; D006360:Heat-Shock Proteins