Colorectal cancer is the third leading cause of cancer-related deaths in humans. The American Cancer association reported the five-year survival rate for rectal cancer patients is only 12%.
Researchers from the University of South Carolina found a potential new target for immunotherapy of colorectal cancer.
Cancer uses tolerance mechanisms to evade our immune system. T cells are immune cells that target killing cancer cells. However, they are also classified into different types, such as a regulatory T (Treg) cell, which ensures that we maintain tolerance to our own cells. Cancer cells increase the presence of Treg cells and are prevented from being killed by other types of T cells.
In a mouse model of colitis, deletion of the GARP gene on Treg cells prevents the intestinal immune system from maintaining optimal tolerance. Without GARP, Treg cells do not effectively suppress the immune system, and they also enter the intestine less. In addition, the team also found that in the mouse model of colon cancer, the deletion of GARP on Treg cells reduced the tumor in mice by half.
"In preclinical cancer models, mice lacking GARP on Treg cells performed better and more T cells infiltrated the tumor," the researchers said. "This seems to happen only in the intestines. When other parts (such as the skin) induce cancer, there is no difference in the presence or absence of GARP on mouse Treg cells."
Studies have shown that another major factor involved in mediating Treg cells is TGF-β. The cells release TGF-β, GARP is involved in TGF-β activation, and TGF-β and GARP together regulate the migration of Treg into the intestine.
If researchers can figure out how colon cancer cells increase the homing of intestinal Treg cells, they can block this homing signal, allowing the immune system to detect cancer and eradicate cancer.
Currently, they believe that the cell surface protein CD103 may be a homing signal. "When the surface of the cell expresses GARP, it grabs TGF-β secreted by other cells," the researchers explained. "The CD103 expression is down-regulated, and CD103 is like the secret code for Treg cells entering the intestine."
"Cell cancer patients have high levels of TGF-β, which can upregulate Treg cells. This may be one of the reasons for their lack of response to PD-1 treatment. However, anti-GARP treatment may be a truly effective way." the researchers said. "We will characterize the presence of GARP on human colon cancer Treg cells to further Treatment target considerations.”
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