A mechanism that offers a promising new approach for harnessing the immune system to fight cancer in mice without triggering autoimmune reactions has been discovered by scientists.
The work by St. Jude Children's Research Hospital scientists focused on white blood cells called regulatory T cells- which serve as the immune system's police force and can interfere with the immune system's ability to fight cancer.
In this study, investigators identified a mechanism that boosts the ability of regulatory T cells to cause problems by blocking an effective anti-tumor immune response. The same process, however, plays no role in maintaining immune balance or preventing the misguided immune attack on healthy tissue that leads to autoimmune problems, researchers reported.
Blocking this mechanism led to the elimination or dramatic reduction of melanoma by the immune system in mice, without causing the autoimmune and inflammatory problems often associated with current cancer-treatment efforts that target immune regulators, scientists said.
The mechanism is built around two proteins. One, semaphorin-4a (Sema4a), is carried on the surface of various immune cells that can spark inflammation. The other, neuropilin-1 (Nrp1), is carried on the surface of regulatory T cells.
Knocking out or blocking the activity of Nrp1 on regulatory T cells in mouse models of several human cancers, including the deadly skin cancer melanoma, led to reduced, delayed or complete elimination of the tumors. Blocking Sema4a had a similar anti-tumor effect, researchers reported.
The study is published in journal Nature.