Blocking GARP–TGFβ axis may be a way to combat cancer
Transforming growth factor beta (TGF-β) is a cytokine that influences the growth and proliferation of many cell types. Regulatory T-cells use it to prevent autoimmunity. However, tumors can hijack this cytokine for their own purposes. As early as the 1980s, scientists noticed the connection between this cytokine and protein. Aggressive tumors have higher levels of TGF-β, which facilitates the growth of tumor cells and suppresses anti-tumor immune responses.
So targeting this cytokine has long been considered as a potential way to combat cancer. Unfortunately, attempts to data have failed because in addition to tumor cells healthy cells also need this cytokine. It is infeasible to completely inhibit it.
To address this problem, a team of researchers led by Dr Zihai Li from Medical University of South Carolina investigated a related protein called GARP. GARP is a receptor and so far it is the only protein that has been found to “dock” TGF-β to the surface of cells, therefore promoting the storage of TGF-β.
The researchers noticed that GARP in samples of human cancers was at very high levels. So they conducted this study to elucidate why this occurs. Mouse experiments showed that deletion of GARP resulted in slower growth rate of mammary tumors and less lung metastasis. When GARP levels were restored in tumor cells, TGF-β signaling, tumor growth, and metastasis were increased.
In mice with breast carcinoma, GARP overexpression promoted Foxp3+ Treg activity, enhancing cancer progression and metastasis. Importantly, treatment with a GARP antibody 4D3 inhibited the spread of primary mammary tumors in mice while did not hamper tumor growth. Treatment with the antibody plus immunotherapy might be able inhibit both the original tumor and metastases.
But one obstacle needed to be overcome: blocking GARP may affect the helpful activity of Tregs — a normal function that prevents autoimmunity.
Overall, the findings define the oncogenic effects of the GARP–TGFβ axis in the tumor microenvironment. Better understanding the axis represents would have diagnostic and therapeutic applications.
The study, titled “Surface Expression of TGFβ Docking Receptor GARP Promotes Oncogenesis and Immune Tolerance in Breast Cancer,” was published 15 December 2016 by American Association for Cancer Research. Cusabio provides you high-quality proteins and antibodies such as polyclonal antibody. Feel free to contact us.
