Immunogenic Fingerprinting in the New Era for Personalized Medicine: Serum Amyloid A and Macrophages in the Tumour-Microenvironment
Prof Anna-Mart Engelbrecht
- Department of Physiological Sciences, Stellenbosch University
Title of the project
Immunogenic fingerprinting in the new era for personalized medicine: Serum amyloid A and macrophages in the tumour-microenvironment
The mediators and cellular effectors of inflammation are important role players of the tumour micro-environment. In some cancer types, inflammatory conditions are present before the malignant change occurs, and in others, an oncogenic change induces an inflammatory micro-environment that promotes the development of tumours. Regardless of its origin, it is now well established that an inflammatory micro-environment promotes tumour growth, however, the molecular pathways of cancer-related inflammation still need to be unravelled. Serum Amyloid A (SAA) is an acute-phase (AP) protein predominantly synthesized by the liver, which belongs to a family of apolipoproteins associated with high-density lipoprotein (HDL) in plasma. SAA has long been investigated as a predictor of cancer risk and as a prognostic marker; it has also been shown that SAA could be used as a biomarker for therapy response, relapse and patient survival rates. Although SAA is primarily expressed in the liver, it has been demonstrated that certain cancer tissue also expresses SAA and that it is associated with poor prognosis and survival in cancer patients. Despite the extensive literature on SAA, a link between SAA and the tumour-associated micro-environment has yet to be established. Although numerous studies have addressed the interaction between the acute phase (AP) immune response and SAA in other inflammatory models, the associated molecular mechanisms and implications thereof in a cancer-specific setting remains unexplored.
The main aims of the project are, therefore, (1) to determine whether colon carcinoma cells express acute phase‐serum amyloid A (AP‐SAA) during inflammatory conditions; (2) to determine the role of APSAA in macrophage recruitment, tumour infiltration and polarization; (3) to assess the role of SAA expression and macrophage infiltration in a tumour‐bearing mouse model, in wildtype (WT) and SAADKO (SAA1‐/SAA2‐) mice; and (4) to assess the immunogenic “fingerprint” (SAA expression and tumour‐associated macrophage (TAM) infiltration) in colitis‐associated cancer (CAC) through the analysis of tumour biopsies obtained from patients.