A team of Chinese researchers has identified a transcription factor that affects the immunologic effects of T cells, providing a new potential target for tumor immunotherapy.
T cells are often called “the workhorses of the immune system” for their critical role in orchestrating the immune response and killing cells infected by pathogens.
One emerging immunotherapy in recent years is CAR-T cells therapy. It separates T cells from a patient’s blood and genetically engineers them to produce receptors on their surface called chimeric antigen receptors or CARs. The special receptors allow T cells to recognize and attach to tumor cells. When the CAR-T cells are infused back into the patient, the engineered cells will multiply in the patient’s body and recognize and kill cancer cells.
However, previous studies found that some T cells can be dysfunctional when they encounter self-antigens or are exposed to chronic infection or tumor microenvironment.
To reveal the molecular mechanism behind T cells dysfunction, researchers from China’s Third Military Medical University and Tsinghua University used an in vitro T cell tolerance induction system in mice and found a high-level expression of transcription factor NR4A1.
NR4A1 is the transcription factor of the nuclear receptor NR4A. Nuclear receptors are a class of proteins that can work with other proteins to regulate the expression of specific genes. A transcription factor is a protein that binds to specific DNA sequences, thereby controlling the rate of transcription of genetic information from DNA to messenger RNA.
The researchers reported on the British journal Nature that over-expression of NR4A1 inhibits T cell function and deletion of NR4A1 overcame T cell tolerance and enhanced immunity against tumor and chronic virus.
They said that the study identified NR4A1 as a key general regulator in the induction of T cell dysfunction, and a potential target for tumor immunotherapy.
In recent years, immunotherapy, therapies that enlist and strengthen the power of a patient’s immune system to attack tumors, has emerged as a new cancer treatment.
In 2017, two CAR-T cell therapies were approved by the U.S. Food and Drug Administration, one for the treatment of children with acute lymphoblastic leukemia and the other for adults with advanced lymphomas.