Figure 1.
Four whole tumor lysate preparations currently in use in the clinics. (A) Hypochlorous acid (HOCl) induces rapid necrotic cell death and enhances the immunogenicity of tumor proteins via oxidation. The increased immunogenicity of HOCl-oxidized tumor proteins are due to a number of mechanisms, including specific binding of oxidized proteins to low-density lipprotein (LDL) receptor to activate dendritic cells (DCs), improved degradation of oxidized proteins by proteinases, improved DC antigen processing and presentation via the major histocompatibility (MHC) molecules, and crosspriming of tumor-specific T cells via T cell receptor (TcR). HOCl might also inactivate IL-10 and transforming growth factor (TGF)-β that can inhibit anti-tumor responses and facilitate T regulatory (Treg) cell proliferation; (B) Ultra-violet B (UVB)-irradiation induces apoptotic tumor cell death. This causes the exposure of phosphatidylserine (PS) and translocation of calreticulin (CRT) to facilitate DC uptake and crosspresentation of the apoptotic tumor cells. The release of high mobility box group-1 (HMGB-1) and pentraxin-3 (PTX-3) by late-stage apoptotic tumor cells can stimulate DC maturation and elicit specific anti-tumor T cell responses; (C) Repeated freeze-thaw treatment of tumor cells induces necrotic cell death and cause the release of numerous danger signals such as HMGB-1, heat-shock proteins (HSPs), DNA, RNA and uric acid that stimulate partial DC maturation. Danger signals such as HSPs, HMGB-1 and uric acid could bind to scavenger receptor-A and toll-like receptor (TLR) 4 on DCs to elicit immune responses; (D) Hyperthermia, which is heat-kill treatment of tumor cells, induces necrotic cell death and increased expression of MICA (major histocompatibility class I chain-related; natural killer group 2D [NKG2D] ligand) and MHC Class I to improved natural killer (NK) cell and antigen-specific CD8+ T cell recognition, respectively.