Examining the role of JAM-A in tumor-educated monocytes. Onderzoek naar de rol van JAM-A in monocyten van tumordragers

Solid tumors contain a variety of non-malignant cells, including immune cells, connective tissue cells and vascular components, collectively termed the tumor microenvironment (TME). Among immune cells, macrophages are particularly abundant, representing 20-60% of all immune cells in a tumor, in some cases being the only immune cell type present in the tumor. Presence of these so-called tumor-associated macrophages (TAMs) in high numbers is generally associated with poor prognosis. Studies using mouse models of cancer provided a mechanistic basis for this by showing that TAMs contribute to tumor progression via multiple ways, including the induction of angiogenesis, promoting local invasion and distant metastasis formation, stimulation of cancer cell proliferation, and inhibition of anti-tumor immune responses. Moreover, TAMs have been reported to promote resistance to a number of anticancer therapies, including chemotherapy, anti-angiogenic therapy, and immunotherapy. These observations make TAMs promising novel therapeutic targets in cancer. Accordingly, the first TAM-targeting drugs, CSF1R inhibitors, showed encouraging results in preclinical studies and already entered clinical trials. Research by our group and others has shown that the primary source of macrophages in tumors are circulating classical monocytes which are recruited to tumors and differentiate into tumor-promoting TAMs. Therefore, we want to understand how the presence of a tumor in the body changes the functional properties of circulating monocytes and identify tumor-induced surface markers or pathways which could be targeted to prevent monocyte recruitment and subsequent TAM accumulation at the tumor site. JAM-A came out as a surface molecule which is upregulated on tumor-educated monocytes. In this project, we aim to analyze its function.