Perforin and granzyme cytolytic pathway

The perforin/granzyme cytolytic pathway is a crucial immune effector mechanism utilized by cytotoxic T lymphocytes and natural killer cells to eliminate virus-infected and malignant target cells. Upon recognition of a target cell, these lymphocytes release cytotoxic granules containing perforin and granzymes at the immunological synapse. Perforin forms pores in the target cell membrane, allowing granzymes (particularly granzyme B) to enter the cytosol, where they trigger apoptotic cell death primarily through activation of caspases and cleavage of intracellular substrates. This rapid and efficient process is essential for immune surveillance and tumor control. Tumor cells may develop resistance by expressing inhibitors such as SPI-6/PI-9 or by down-regulating pathways essential for pore formation or granzyme activity. While the pathway is not itself a single therapeutic target, its components, especially perforin and granzymes, are of significant interest in cancer immunotherapy and immune modulation research. Off-target effects and immunopathology represent principal safety challenges in therapies that enhance this cytolytic function.

Other names

Perforin/granzyme pathwayGranule exocytosis cytotoxicityCTL/NK cell cytolytic pathway

Perforin forms pores in the target cell membrane, allowing granzymes (primarily granzyme B) to enter the cytosol and trigger apoptosis via caspase activation. Alternative mechanisms: Granzymes can also induce non-cytotoxic immune signaling, and other cytolytic proteins (e.g., FasL) can complement or substitute this pathway.