New revolution in immunology : PDAC model

Pancreatic ductal adenocarcinoma (PDAC) is a lethal disorder and one of the most common cancer subtypes today, especially in the developed world. It is an aggressive solid malignancy characterized by painless expansion, rapid progression through metastasis and absence of distinct symptoms. These clinical features lead to delayed diagnosis, mostly, at a late metastatic stage. Only 20% of patients with PDAC can be treated [1]. The existing treatment regime includes surgical removal (resection) of the tumor along with chemotherapy. Resistance to chemotherapy and radiation therapy is a major problem seen. This arises due to the complex tumour microenvironment (TME) which is characterized by epithelial-to-mesenchymal transition (EMT), desmoplasia of the stroma and evasion of tumour surveillance leading to a multistage interaction between the neoplastic and stromal cells [1-3]. Pancreatic stellate cells are the major orchestrators of desmoplasia in PDAC. The contribution of PSCs to the development of the tumor microenvironment is manifold. The PSCs differentiate into cancer-associated fibroblasts (CAFs) which produce desmoplastic stroma and two sub-populations of CAFs exist. One sub-population expresses elevated levels of α-smooth muscle actin (α SMA) while the other one distantly situated from neoplastic cells express low levels of α SMA and produce IL-6 which promotes cancer progression and immune suppression. Activated PSCs express cytokines, chemokines and adhesion molecules that regulate T-cell migration that are involved in immune-surveillance. CXCL12 secreted by activated PSCs serve as a chemoattractant for CD8+ T cells which show pronounced chemotaxis towards the activated PSCs [4]. Biomarkers and signaling pathways useful in PDAC for immunoprofiling.