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Immunogenicity of 56°C and UVC‐treated prostate cancer is associated with release of HSP70 and HMGB1 from necrotic cells
Author(s) -
Brusa Davide,
Migliore Elisa,
Garetto Stefano,
Simone Mariagrazia,
Matera Lina
Publication year - 2009
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.20981
Subject(s) - lncap , propidium iodide , intracellular , prostate cancer , extracellular , cancer research , chemistry , apoptosis , biology , programmed cell death , medicine , cancer , microbiology and biotechnology , biochemistry
BACKGROUND Prostate hyperthermia and photodynamic therapy can be delivered by a variety of procedures which result in a wide range of temperatures and light energy and cause different kinds of cell death. METHODS We have addressed the immunogenic effect of heating and UVC irradiation on the prostate cancer (PCa) cell line LNCaP, by studying the release of Danger Associated Molecule Pattern (DAMP) molecules HSP70 and HMGB1 and the dendritic cell (DC) antigen‐presenting efficiency. RESULTS Intracellular upmodulation and extracellular release of HSP70 were inversely correlated. Mild temperatures (43–47°C) induced an early increase of intracellular HSP70, whereas the highest temperature (56°C) induced its extrusion from the cell. Likewise, UVC caused an immediate migration of HSP70 into the cell medium in the absence of any intracellular modulation. 56°C and UVC also induced a robust release of HMGB1. The release of DAMP molecules was closely associated with post‐apoptotic membrane damage, as shown by double Annexin V/propidium iodide staining, whereas β‐tubulin, a structural component of cell membranes, was specifically induced by 56°C heating. Tumor uptake strongly impaired the cytokine‐driven maturation of DCs and 56°C heating led to a significant recovery of CD83 and CCR7 DC maturation markers, but did not influence the antigen cross‐presentation activity. On the contrary, UVC‐treated LNCaP had negligible effects on DC maturation, but increased the cross‐priming of tumor specific CTL. CONCLUSIONS These data may be of use in the design of effective non‐surgical PCa ablations that combine tumor destruction with long lasting immunity. Prostate 69:1343–1352, 2009. © 2009 Wiley‐Liss, Inc.