JAN 22, 2020

How the VISTA molecule affects immune responses

WRITTEN BY: Kathryn DeMuth Sullivan

A new study describes how a molecule named VISTA has been impeding immune responses in cancer therapies. By turning this molecule “off,” researchers from Dartmouth Hitchcock's Norris Cotton Cancer Center have figured out how to improve immune responses in patients receiving anticancer treatments. The study was published under the title, "VISTA, a checkpoint regulator of naïve T-cell quiescence and tolerance in the periphery” in the journal Science.

"We have learned that keeping your immune system quiet is a challenging and very active process," says lead investigator Randolph Noelle, PhD. "VISTA mediates immune system function and its loss can result in the development of unwanted immune responses. But VISTA may also be a valuable target in regulating the immune response in cancer and autoimmunity."

VISTA is what scientists call a negative checkpoint regulator. That means that it tempers the immune system in order to stop the activation of self-antigens like cancer cells. "Like other negative checkpoint regulators, blocking VISTA in cancer may enhance the host's ability to make protective tumor-specific immune responses," says Noelle.

Noelle and the team of researchers have been working on understanding the role of the VISTA molecule, which stands for V-domain Ig suppressor of T-cell activation, for almost ten years. Finally, as the authors write in the study, they have something to show for all their hard work:

“Therapeutic targeting of VISTA using an agonistic antibody in mice curbed the development of graft-versus-host disease and promoted the death of naïve T cells abnormally activated by self-antigen. VISTA thus represents a distinctive immunoregulatory molecule that controls naïve T cell function by maintaining quiescence and peripheral tolerance.”

The researchers hope to use this finding to run clinical trials to determine if their research can be used outside of mice in human patients with cancer. As Science Daily reports, if this is possible, “this antibody may be valuable in the development of drugs and vaccines to provide therapeutic response to cancer and cancer cures.”

Sources: Science, Science Daily