Will the CD70/CD27 pathway pave the way as target for immunotherapy in colorectal cancer?

Cancer cells are embedded in stroma, the connective tissue framework of solid tumors. The mutual and interdependent interactions between the cancer cells and their microenvironment (TME) are increasingly recognized as effective targets for cancer therapy. The most abundant cells in the TME are the cancer-associated fibroblasts (CAFs). Although it has been shown that CAFs play an important role in the proliferative and invasive behavior of colorectal cancer (CRC), CAFs represent a heterogeneous population with both cancer-promoting and cancer-restraining actions, lacking specific markers to target them. Although absent from normal tissue, various tumor types have shown expression of CD70 on the malignant cells. It has been demonstrated that these CD70-positive tumor cells can suppress the immune system by inducing an accumulation of the immune suppressive regulatory T cells (Tregs). In this study, we will be the first to determine the role of CD70 in CRC, not merely focusing on the tumor cells but also taking the TME into account. Our preliminary data point towards the expression of CD70, not on the tumor cells itself but on the CAFs in CRC. Moreover, our results have shown that the presence of CD70 on the CAFs was associated with poor prognosis of the patient. In this project, we will further investigate the role of CD70-positive CAFs in CRC. Thereby, we will assess the migratory and invasive properties of CD70-positive CAFs and investigate its effect on the tumor cells. In addition, we will determine whether expression of CD70 on CAFs enhances immune suppression by the accumulation of Tregs. These experiments will lead to the completion of a PhD.

Keywords:COLORECTAL CANCER

Disciplines:Morphological sciences, Oncology