In early tumourigenesis, immune cells, including CD8+ T cells, detect danger signals from cancer cells and respond by eliminating these cells, leading to tumour immunogenicity. Dendritic cells are key regulators of tumour-specific immune responses in that they function as antigen presenting cells, activating CD8+ cytotoxic T lymphocyte (CTL) responses or stimulating CD4+ T cells through interaction with major histocompatibility complex (MHC) class II molecule-antigen complexes (Finn 2008). In pancreatic tumourigenesis, Hiraoka and colleagues reported that chemokine CXCL17 was responsible for infiltration of immature dendritic cells while ICAM-2 permitted killing of tumour cells by CD8+ cells. During evolution from precursor lesions to PDAC they found that the host immune response was tempered and tumours developed immune tolerance by downregulating CXCL17 and ICAM-2 (Hiraoka et al. 2011). Interestingly, Dillman and colleagues recently described the value of reintroducing dendritic cells loaded with antigen from autologous irradiated tumour cells in metastatic melanoma. Those patients who received this dendritic cell vaccine survived significantly longer than irradiated tumour cell vaccine alone (Dillman et al. 2011). Conversely, in PDAC, blockade of TLR4 signalling enhanced dendritic cell-mediated recruitment of T helper 2 (Th2) CD4+ cells, and this resulted in increased pancreatic inflammation and accelerated tumour progression (Ochi et al. 2012a). Thus depending on antigenic stimulus, dendritic cells can both promote and inhibit tumour progression. Promotion of anti-tumoural cell mediated responses, such as are generated through effective tumour immunosurveillance are being pursued in cancer. These strategies focus on engaging T cell responses in a field referred to as cancer immunology. The use of tumour antigen based vaccines and T cell adoptive transfer has provided some success in a small cohort of patients, however, the majority fail to respond clinically. More successful has been the use of T cell checkpoint inhibitors, to promote T cell activation. CTLA4 inhibitors such as ipilimumab and Programmed cell death 1 (PD1)/Programmed cell death ligand (PDL1) checkpoint inhibitors may be used to enhance CTL responses. Indeed the advances that these drugs have made in the field of metastatic melanoma have been striking. CTLA4 is a CTL surface protein and functions as a negative regulator of T cell function. CTLA4 interacts with APC membrane bound co-stimulatory molecules and functionally competes with the T-cell co-stimulatory molecule CD28. Thus ipilimumab binds and inhibits CTLA4 releasing a break to T-cell co-stimulation. Ipilimumab was the first agent to prolong overall survival in metastatic melanoma. CTLA4 is not the only improvement in the understanding of checkpoint biology. PD1 is an inhibitory receptor which following chronic T cell activation is induced via ligands including PDL1. Production of PDL1 by tumour associated macrophages or tumour cells themselves permits immune evasion by this mechanism (Sullivan et al. 2013), thus making it an exciting target for therapy. Trials in melanoma thus far have shown reliable tumour responses in at least 50 % of cases.

Commonly difficulties with these types of therapies arise when there are insufficient T lymphocytes infiltrating tumours to activate. Indeed, certain authors have suggested that high T cell infiltrate denotes good prognosis in these patients, while low infiltrate suggests failure of this strategy (Gajewski and Schumacher 2013). Two major mechanisms of immune resistance appear to exist in this context: failure of T cell trafficking; and immune suppression within the microenvironment. It may be hypothesised that removal of immunosuppressive cells such as bone marrow derived cells (BMDCs) and macrophages from the tumour microenvironment may allow activation of a more sustained T cell response.