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Anti-tumor immunity is stimulated after PDT for cancer due to the acute inflammatory response, exposure and
presentation of tumor-specific antigens, and induction of heat-shock proteins and other danger signals. Nevertheless
effective, powerful tumor-specific immune response in both animal models and also in patients treated with PDT for
cancer, is the exception rather than the rule. Research in our laboratory and also in others is geared towards identifying
reasons for this sub-optimal immune response and discovering ways of maximizing it. Reasons why the immune
response after PDT is less than optimal include the fact that tumor-antigens are considered to be self-like and poorly
immunogenic, the tumor-mediated induction of CD4+CD25+foxP3+ regulatory T-cells (T-regs), that are able to inhibit
both the priming and the effector phases of the cytotoxic CD8 T-cell anti-tumor response and the defects in dendritic cell
maturation, activation and antigen-presentation that may also occur. Alternatively-activated macrophages (M2) have also
been implicated. Strategies to overcome these immune escape mechanisms employed by different tumors include
combination regimens using PDT and immunostimulating treatments such as products obtained from pathogenic
microorganisms against which mammals have evolved recognition systems such as PAMPs and toll-like receptors
(TLR). This paper will cover the use of CpG oligonucleotides (a TLR9 agonist found in bacterial DNA) to reverse
dendritic cell dysfunction and methods to remove the immune suppressor effects of T-regs that are under active study.
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