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Response to sublethal heat treatment of prostatic tumor cells and of prostatic tumor infiltrating T‐cells
Author(s) -
Kramer Gero,
Steiner Georg E.,
Gröbl Marion,
Hrachowitz Kristian,
Reithmayr Franz,
Paucz Ljubomir,
Newman Martin,
Madersbacher Stephan,
Gruber Diego,
Susani Martin,
Marberger Michael
Publication year - 2003
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.10314
Subject(s) - lncap , cytokine , hyperplasia , cancer research , immune system , prostate , heat shock protein , tumor necrosis factor alpha , downregulation and upregulation , immunotherapy , hyperthermia , medicine , antigen , pathology , biology , immunology , cancer , biochemistry , gene
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‐γ, TNF‐α) 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. © 2003 Wiley‐Liss, Inc.