A gene has found to drive cancer immune responses


Cancer has shown an outbreak in recent years, regardless of age or gender. Cancer is one of the major diseases that currently seriously affect human health and threaten human life. And cancer is one of the biggest causes of death in all countries of the world today. Therefore, the World Health Organization and various government departments have made it a priority to overcome cancer.

Traditional treatments for cancer include surgery, chemotherapy, and radiation therapy. However, the efficacy of these several therapies is minimal, and the side effects of chemotherapy and radiotherapy are more obvious. With the continuous advancement of medicine, the fourth cancer therapy, immunotherapy, is gradually emerging.

In general, the human immune system recognizes cancer cells and kills them. However, cancer cells bind to PD-1 on the surface of immune cells by expressing a large amount of PD-L1 protein,  transmitting a false signal to immune cells: they are good cells and do not attack them. This process is also known as an immune escape. This is one of the reasons why cancer cells can survive.

Immunotherapy targets and destroys cancer cells by enhancing the body's own immune system. It is one of the most promising frontiers in cancer research, but many patients do not respond to these therapies. The reasons are not fully understood.

Scientists at the Yale Institute of Systems Biology have used genome-scale in vivo CRISPR screens to analyze genes that drive tumor formation in hosts with different levels of the immune response. The study was published in the journal Cell System.

Their research represents that they are closer to understanding how the cancer cell's genome directs cancer formation and affects the microenvironment of the tumor.

Led by Sidi Chen, an assistant professor of genetics at Yale University School of Medicine, scientists mapped the genes of mice to identify genes that are known to be potentially important for cell attack or immune acquisition.

They discovered a little-known single gene PRKAR1A. When they deleted the gene in cells, causing rapid tumor formation, which exceeded all other tested genes. When the gene was removed, the gene also altered the tumor environment, increased inflammation and changed the immune response.

Their findings suggest that tumor-specific mutations in this particular gene dramatically alter the genetic program of cancer cells and reshape the microenvironment of the tumor.

The researchers thought how cancer cells evade detection by the immune system and which genes activate pathways that suppress the immune system are associated with different types of cancer.

This little-known gene is expected to provide researchers with a deeper understanding of how different types of immunosuppressive cells are recruited into tumors, and how related changes is helpful to classify patients' responses to the different types of immunotherapy.
 
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