Protein Critical to Immune Response Discovered

Researchers in a new study have found a regulator of immune responses that explains why T cells do not stop chronic infections and destroy tumors.

"We discovered that a protein on the surface of T cells, P-selectin glycoprotein ligand-1 (PSGL-1), acts as a negative regulator of T cell function," said researcher Linda Bradley, PhD. "PSGL-1 has the broad capacity to dampen T cell signals and promote the exhaustion of T cells in viral and tumor mouse models."

The response of T cells falls short when it comes to chronic infections and cancers that create T cell dysfunction.

Drugs that block immune checkpoints have improved treatments for certain cancers. These checkpoints restrain the immune system from attacking itself and prevent autoimmune diseases.

Inhibiting these checkpoints allows the immune system to forcefully attack the cancer and could extend survival, according to the study published in Immunity.

Researchers discovered that PSGL-1 is critical for increasing levels of immune checkpoints. When PSGL-1 is absent, T cells are active for a longer period of time than normal.

"Blocking PSGL-1 may enhance the immune response to cancer and chronic viral infections such as hepatitis. In contrast, activating PSGL-1 may be a way to inhibit immune responses that could potentially be used to treat autoimmune diseases, such as rheumatoid arthritis, psoriasis, multiple sclerosis and lupus," Dr Bradley said.

Mice lacking PSGL-1 were able to clear lymphocytic choriomeningitis virus (LCMV) that typically lasts for months.

"Total clearance of LCMV is rare," Dr Bradley said. "When we saw that, we knew PSGL-1 was crucial for limiting immune responses."

The mice were then injected with melanoma cells and found that the tumors grew at a much slower pace than they do in normal mice, the researchers wrote.

Researchers are currently looking for anti-cancer drugs that would be able to work in combination with PSGL-1 inhibitors to make the approach more lethal for tumor cells.

"We've received a lot of interest from pharmaceutical companies wanting to explore the clinical potential of our findings," Dr Bradley concluded. "PSGL-1 inhibitors could provide another tool in the arsenal against cancer, and benefit the many patients who don't respond to the currently available checkpoint inhibitors."