Specific CD4 T Cells Key to Initiating Antitumor Immunity

Researchers in Washington have discovered that a type of white blood cell once thought to be just an immune system helper also plays a role in triggering the body’s defenses against cancer. They believe the findings could lead to more effective cancer immunotherapies.

Immunotherapy is relatively new and has shown promise in curing a range of cancers, but is unsuccessful for many patients. Many of these immunotherapies focus primarily on the role of one type of T cells, called CD8-positive T cells.

However, a new animal study from researchers at Washington State University (WSU) could help boost favorable immunotherapy response with new insights into the mechanisms that help start the body’s immune defenses against cancer.

“One of the most challenging parts of current cancer immunotherapy is the low response rate,” says Hui Zhang, a  WSU assistant professor of pharmaceutical sciences and lead author of the study. “The lack of knowledge of how to enhance lymphocyte infiltration into the tumor hampers the success of improving the response rate to cancer immunotherapy. Our finding shows promise in solving this problem.”

The immune system has two types of killer cells: CD8-positive T cells, and natural killer cells. Both can attack virally infected cells and cancer cells. Natural killer cells are innate and roam around the body. They act as the first line of defense in our immune system but cannot recognize specific antigens on their own. After the natural killer cells start to work, the CD8-positive T cells, which can recognize specific antigens, arrive. While CD8-positive T cells and their mechanisms have been well studied and are used in current immunotherapies, not much is known about how to activate natural killer cells’ antitumor function.

The WSU team found that a population of T cells called CD4-positive helper T cells play a role in starting a chain of antitumor immunity defenses that allow killer cells to better infiltrate melanoma and breast cancer tumors.

Using genetic knock-out mice experiments, Zhang’s group found evidence that a certain type of CD4-positive T cells, called tissue-resident memory T cells, may be critical in activating those first lines of natural killer cell defenders. Their experiments showed that they were effective against both melanoma and breast cancer tumors.  The specific CD4 T cells together with the natural killer cells not only killed tumor cells and controlled tumor progression but also enhanced infiltration of other white blood cells into the tumor.

In future studies, the researchers plan to continue to investigate the precise cellular and molecular mechanisms of this antitumor immunity—first in mice to develop an effective cancer immunotherapy. Then, the team hopes to move on to clinical trials in human subjects. “Our goal is to develop a powerful cancer immunotherapy approach that is effective for all patients with different types of cancer,” said Zhang.

The findings were published recently in The Journal of Immunology.