B7 immune checkpoint proteins as novel therapeutic targets in cancer
Immunotherapies 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 group 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 alternative B7 immune checkpoint proteins as novel biomarkers and therapeutic targets in cancer, by unraveling their functions and their relation to tumorigenesis.
We have contributed knowledge on miRNA regulating B7-H3, and its clinical implications in breast cancer, and deciphered the role of B7-H3 in glycolysis and sensitivity to chemotherapy and targeted drugs in breast cancer and melanoma, as well as discovered molecular mechanisms underlying the chemo-sensitive role of B7-H3. We have also described correlation of B7-H3 expression with poor outcome in prostate cancer, and provided important knowledge on the role of B7-H4 in sensitivity of renal cancer cells to targeted therapies.
You can read more about our recent findings in this blog post and in our reviews on B7-H3 in human cancer beyond immune regulation, and on the hopes of targeting B7-H3 in neuroblastoma.
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.