Targeting Sema5B in RCC Immunotherapy
Abstract
The kidney removes wastes from our body and maintains a healthy balance of water, salts, and minerals. When we are exposed to toxins, our two kidneys help eliminate them from our bodies as well. Hence, the toxins, one point in time, travel through the kidneys increasing the chance of kidney cancer. Exposure to toxic chemicals while on base or during deployment can lead to kidney cancer among a great deal of Veterans. Not only Veterans but any other people can be diagnosed with kidney cancer in their lifetime for some known and unknown reasons. In the United States, kidney cancer is among the top ten malignancies in both men and women. Often the disease is diagnosed at an advanced stage when it spreads to the other organs (metastasis) leading to their death in 2-3 years. In recent years, immunotherapy seems to be a promising way to treat advanced-stage and metastatic kidney cancer patients. Immunotherapy is a type of cancer treatment that boosts the body s natural defenses (immunity) to fight cancer. Our body s immunity is maintained by many types of cells, called immune cells. The immune cells keep themselves from attacking normal cells in the body by checkpoints. Kidney cancer cells sometimes use these checkpoints to avoid being attacked by the immune system. Immunotherapies are designed to inhibit the checkpoints so the immune cells can kill the cancer cells. Blocking checkpoints might lead the immune cells to kill our normal cells, as well, which is called autoimmunity, and this is even worse if the patients have preexisting autoimmune disorders. Moreover, kidney cancer cells develop unique mechanisms to develop resistance against these checkpoint inhibitors. In fact, only a small percentage of kidney cancer patients have benefited from immunotherapy, which urges researchers to develop highly specific and targeted immunotherapies for the disease. Semaphorins are the proteins found in many parts of our body where they serve many similar or different biological functions. There are many types of semaphorins in our system. Semaphorin 5B (Sema5B) is known to eliminate cell-to-cell communications in our nerve cells, thereby regulating wrong nerve signals. Interestingly, Sema5B level is highly elevated in kidney cancer cells compared to any other parts of our body. Immune cells must contact tumor cells to initiate their killing. Given the high Sema5B content in kidney cancer cells and its ability to prune cell-to-cell contact, the cancer cells will likely avoid contacting immune cells, eventually making them safe from being killed by the immune cells. The proposal is a proof-of-principle study to know whether Sema5B helps kidney cancer cells to escape from immune cell-mediated killing. The knowledge gleaned from this proposal will be important to develop novel immunotherapy against kidney cancer and, given that Sema5B level is highest in kidney cancer tissues compared to any other normal parts of our body, the therapy will have minimum off-target toxicity.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310339
Entities
People
- Anirban Kundu
Organizations
- United States Army
- University of Alabama at Birmingham