How a lipid secreted by cancer tumours stops the immune system from mounting an immune response against it was discovered by T cell researchers.
When lysophosphatidic acid (LPA) binds to killer T cells, it acts almost like an "invisibility cloak," preventing T cells from recognizing and attacking nascent tumours.
Senior author Raul Torres, PhD, professor of immunology at National Jewish Health, said that in recent years, several therapeutic medicines have been developed that spur a person's own immune system to fight cancer.
Scientists have known that LPA is secreted by many types of cancer cells, appears to promote the growth and spread of tumor cells, and that immune cells known as CD-8 "killer" T cells have several receptors for LPA. Killer T cells can destroy cancer cells when activated against them.
Researchers led by Dr. Torres showed that LPA keeps T cells inactivated even after they have "seen" a target, or antigen, on a cancer cell that would normally trigger an immune response.
They identified the LPA5 receptor as the specific receptor responsible for inhibiting the immune response. In cell cultures and in mice LPA prevented signaling within cells, the appearance of molecules associated with T-cell activation, and proliferation of the T cells.
When they transferred T cells lacking the LPA5 receptor into mice with cancer, tumor growth essentially halted.
The study has been published in journal Cancer Immunology Research.