Granzyme A (GzmA) is a serine protease predominantly found in the granules of cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells. It plays a critical role in immune defense by inducing cell death, both apoptotic and non-apoptotic, in target cells such as virus-infected or cancerous cells. Granzyme A is known to specifically target and cleave a range of important human proteins, including histones, nuclear envelope proteins, and key DNA repair proteins like Ku70 and PARP-1. Additionally, it can activate interleukin-1, contributing to pro-inflammatory activities. Recent research has highlighted Granzyme A's ability to trigger a novel programmed cell death pathway, pyroptosis, by cleaving Gasdermin B (GSDMB), which leads to the release of its N-terminal pore-forming fragment and subsequent cell death. This mechanism is particularly relevant in the context of anti-tumor immunity, as it suggests a new way in which cytotoxic lymphocytes can eliminate target cells. The discovery of Granzyme A's role in pyroptosis has provided new insights into the mechanisms of cell death induced by the immune system and offers potential therapeutic targets for enhancing anti-tumor immunity.
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