Targeting the tumor microenvironment in human pancreatic cancer
Pancreatic cancer (PC) is the third major cause of cancer-associated mortality, with overall poor prognosis with high resistance to conventional therapies including chemotherapy and radiotherapy. PC harbors multiple genetic and epigenetic alterations and has a complex and immune suppressive tumor microenvironment. These factors result in an overall 5-year survival rate of <7%. Immune suppressive cells like myeloid-derived suppressor cells (MDSC) and tumor-associated macrophages (TAMs) represent a major inflammatory component of the stroma in many tumors and expansion of these cells is associated with poor prognosis in cancer patients with PC. Our preliminary data show an increased expression of a scavenger receptor called macrophage receptor with collagenous structure (MARCO) specifically on the suppressive myeloid compartment. Here, we suggest to study the location of MARCO+TAMs and their cross-talk with other immune cells in the tumor microenvironment and how it impact PC progression. Importantly, we will evaluate the potential of in house developed anti-MARCO antibodies. Our data will increase the knowledge of the clinical value of these treatments. |