The Role of Exosomes in the Stip1-Mediated Immune Modulation in Ovarian Cancer

Although the incidence of ovarian cancer ranks the seventh in female cancers, it results in the highest cancer death in women. During tumorigenesis, cancer cells critically interact with its microenvironment that is composed of fibroblast, immune cells, epithelia, and mesenchymal stem cells. Being originated from intracellular organelles, exosomes are extracellular vesicles with diameter ranging from 50 to 150 nm. Cancer cells employ exosomes to deliver mRNA, miRNA, and protein molecules to modify the microenvironments, promoting the growth of cancer cells. To circumvent the host immune surveillance, cancer cells should be able to modify the immune system. For instance, cancer cell’s exosomes induce apoptosis of T cells and promote the production of Treg cells. Using exosomes, cancer cells can deliver FasL, TGF-β, NKG2D ligands, galectin-9 and HSP72 to evade the immune surveillance. Our research team has reported that ovarian cancer cells increase the expression of stress-induced phosphoprotein 1 (STIP1), which is secreted into the blood circulation, resulting in that the STIP1 serum levels are higher in the patients with ovarian cancer than in control individuals. STIP1 stimulates cancer cell growth by activing ERK, and the blockade of the STIP1 binding to cancer cells inhibits cell growth. According to current reports, ovarian cancer cells likely modify the microenvironment via the use of exosome. Our working hypothesis is that STIP1 may play a role in the exosome-mediated immune evasion mechanisms. Our preliminary results revealed that treatment with recombinant human STIP1 inhibits the maturation of dendritic cells, which may result in the suppression of T cell activation. In this 3-year project, we plan to: (1) identify the presence of STIP1 in the exosomes of ovarian cancer cells, (2) test the in vitro effects of STIP1 on immune cells, (3) analyze the role of STIP1 in interactions among ovarian cancer cells and immune cells, and (4) develop a novel therapeutic strategy by targeting STIP1 in ovarian cancer.

Project ID:PC10708-1049
External Project ID:MOST107-2314-B182-039