Researchers from Stanford University and New York University have reported that inhibiting the protein LAG-3, often called the immune system brake, can boost the effectiveness of cancer therapies. The study was published in the Proceedings of the National Academy of Sciences (PNAS) and adds a new layer to our understanding of how immune checkpoints influence treatment outcomes. [Source: PNAS, 2024]
The team explains that tumor cells in several cancer types can seize immune-regulating proteins, sometimes referred to as brakes, which normally help immune cells distinguish threats from healthy tissue. When cancer cells absorb these proteins, they gain a protective advantage. This dynamic can accelerate tumor growth and diminish the success of immunotherapies. The findings underscore the delicate balance the immune system maintains and highlight how tumors can tilt this balance in their favor. [Source: PNAS, 2024]
In their investigations, scientists characterized LAG-3 as a molecule with a distinctive, spindle-shaped architecture. They demonstrated that LAG-3 forms a functional dimer, composed of two monomer units that come together to regulate immune signaling. A pivotal aspect of the dimer’s activity is the sugar residue located at its interface, which helps stabilize the interaction and control the protein’s function. These structural insights lay the groundwork for designing more precise interventions that can modulate LAG-3 activity in cancer therapy. [Source: PNAS, 2024]
The researchers further explored how an antibody, used in animal studies for many years to validate experimental therapies, can impede LAG-3 by wedging into the space between the two monomers of the dimer. By effectively blocking this interface, the antibody diminishes LAG-3’s ability to dampen immune responses. The study suggests that such blockade could heighten the impact of various cancer treatments, including surgical, chemical, and immunological approaches, potentially improving patient outcomes. [Source: PNAS, 2024]
These advances come amid ongoing efforts to identify the most challenging cancers to detect and treat. The new findings about LAG-3 offer a potential pathway to enhance the effectiveness of existing therapies and to inform the development of combination strategies that leverage immune modulation. As research progresses, clinicians and researchers may be able to tailor treatments that more precisely disrupt tumor defenses while preserving normal immune function. [Source: PNAS, 2024]