Induction of anti tumour immune response. Once a tumour has escaped immune surveillance, other physiological mechanisms are required to recognise the neoplasm and instigate an immune response against it. However, the immune system has evolved primarily to protect the host from infectious pathogens. Innate immune cells which patrol tissues such as macrophages (MФ) and dendritic cells (DCs), are activated through a broad family of cellular receptors known as pattern recognition receptors (PRRs). These PPRs, are activated by highly conserved pathogen-associated molecular patterns (PAMPs) associated with viruses, bacteria, fungi and other pathogens (Xxxx e Xxxxx, 2001). Once activated MФ, and DCs act as antigen presenting cells (APCs), presenting self and foreign peptides to the adaptive arm of the immune system to invoke a specific and robust response against the pathogen. Because tumours are sterile and derived from host cells, these PAMPs are not present, and despite the presence of APCs and other leukocytes in the tumour microenvironment, PRRs do not become activated and there is a failure to illicit an adaptive immune response. APCs express high levels of MHC class II, which when loaded with pathogen derived antigen (e.g. from phagocytosis) can interact with the CD4 receptor and the cognate T cell Receptor (TCR) on CD4 T cells. When combined with the appropriate secondary activation signal, this interaction results in the activation of the CD4 T cell. Alternatively, endogenous antigen resulting from viral infection, or (via cross presentation) exogenous antigen, can be presented in the context of the MHC class I molecule, which interacts with CD8 and the cognate TCR on a CD8 T cell. This results in the activation of CD8+ cytotoxic T cells (CTL). As host cells bear MHC class I at their surface, activated CTLs are highly specialised to bind to and kill infected self-cells in an antigen specific manner (Xxxxx, 1994). In the context of cancer, immunity has to be initiated against cells expressing tumour- associated antigens (TAA); peptides derived from self-proteins commonly associated with specific tumour types, and which are presented in the context of MHC cIass 1 molecules at the surface of tumour cells. As in the case of a viral infection, a robust response by CTLs is desirable to destroy tumour cells (Xxxxxx et al., 2002, Xxxxx et al., 2000). However, due to the lack of PAMPs and therefore of immune activation of APCs, there is frequently a failure to elicit robust TAA-sp...
