July 13, 2024

New Discovery Protein VISTA Inhibits T-cell Function in Immunotherapy through Interaction with LRIG1

A recent study published in Science Immunology led by researchers and physicians from the Cleveland Clinic has revealed that the immune checkpoint protein VISTA can directly inhibit the functioning of tumor-fighting T-cells during immunotherapy.

The scientists found that VISTA binds to a protein called LRIG1 in T cells, which was previously believed to only promote bone and fat development. This interaction, however, sends signals that suppress T cell replication, survival, and function. This inhibition can occur between molecules on tumor cells and T cells, healthy cells and T cells, and even on the same T cell.

The preclinical findings suggest that blocking LRIG1 function could potentially halt tumor growth in various cancers. In human melanoma and endometrial cancer, LRIG1 expression in tumor-associated T cells was linked to resistance to Immunotherapy.

Under normal circumstances, VISTA plays a role in modulating the immune responses of healthy cells to prevent them from attacking our own bodies, thereby protecting us from autoimmune issues. However, research led by Li Lily Wang, Ph.D., of Cleveland Clinic, has shown that during immunotherapy, VISTA impairs immune activation and prevents T cells from attacking cancer cells.

Pharmaceutical companies have attempted to develop therapeutics to block VISTA during immunotherapy, but progress has been limited due to a lack of understanding of the exact mechanism by which VISTA functions.

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1. Source: Coherent Market Insights, Public sources, Desk research
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