Granzyme-mediated cytotoxicity

Granzyme-mediated cytotoxicity is an essential immune defense mechanism whereby cytotoxic T lymphocytes and natural killer cells eliminate virus-infected cells, tumor cells, and other abnormal targets by releasing specialized secretory granules containing perforin and multiple serine proteases called *granzymes* into the immunological synapse formed with their target. Perforin forms pores in the target cell membrane that allow entry of granzymes into the cytosol. Once inside, different granzymes trigger programmed cell death through various mechanisms: • Apoptosis: Most notably via caspase activation by Granzyme B. • Pyroptosis: Via cleavage/activation of gasdermin family members by certain granzymes such as Granzyme A. • Disruption of DNA repair pathways. • Induction/inhibition of inflammatory responses depending on context. This process is critical for controlling infections and preventing malignancy but can also contribute to pathological inflammation if dysregulated.

Other names

Granule exocytosis pathwayCytolytic granule-mediated cell deathPerforin/granzyme pathway

For drugs targeting this system indirectly (e.g., immune checkpoint inhibitors): - Enhancement of T cell/NK cell activation increases release of perforin and granzymes. - Potential future approaches may include direct inhibition/activation of specific granzymes.