Immune checkpoint protein B7-H3 as novel therapeutic target in cancer

PI: Caroline E Nunes-Xavier
Immunotherapy targeting immune checkpoint proteins are therapeutic approaches that mobilize the immune system to kill the cancer cells. Current therapies use monoclonal antibodies that block receptor-ligand interactions and prevent inhibitory actions on the anti-tumor immune response. Even though a high percentage of patients respond to therapy and obtain long-lasting responses, many patients do not respond or develop therapy resistance, emphasizing the need for novel and more effective treatments. To develop new alternative and improved immunotherapies, it is critical to understand the molecular mechanisms underlying the functional activity of the immune checkpoint proteins. One of our research interests is to validate the immune checkpoint protein B7-H3 as a novel biomarker and therapeutic target in cancer, by unraveling its function and its relation to tumorigenesis.
We have contributed knowledge on miRNA regulating B7-H3, and its clinical implications in breast cancer, in deciphering the role of B7-H3 in glycolysis and sensitivity to chemotherapy and targeted drugs in breast cancer and melanoma, and more recently discovered molecular mechanisms underlying the chemo-sensitive role of B7-H3.

Figure: The B7 proteins are shown with the co-inhibitory receptors they interact with on T cells. Unknown receptors are indicated with a question mark. Proteins targeted by immunotherapy are shown bound to an antibody molecule. TCR: T cell receptor; MHC: major histocompatibility complex. (click to enlarge image)
Read more about our recent findings in this blog post and in our reviews on B7-H3 in human cancer beyond immune regulation.