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<p>Pyroptosis is a form of programmed cell death driven by inflammatory caspases (caspase-1/4/5/11). Distinct from apoptosis, pyroptosis is characterized by the formation of membrane pores, cell swelling followed by rupture, and the release of cellular contents, along with the secretion of a wide range of pro-inflammatory cytokines. Pyroptosis can be activated through two primary pathways: the canonical pathway (caspase-1-dependent) and the non-canonical pathway (caspase-4/5/11-dependent). In recent years, the role of pyroptosis in tumor initiation, progression, and therapy has drawn significant attention, revealing its dual regulatory effects—both anti-tumor and tumor-promoting—highlighting its potential as a novel therapeutic target. Given its pivotal role in modulating anti-tumor immunity, the induction of pyroptosis emerges as a promising strategy to enhance the effectiveness of immunotherapy. To date, an increasing number of studies have explored the synergistic potential of combining pyroptosis-inducing strategies with immunotherapy, particularly immune checkpoint blockade, in cancer treatment.This review explores the molecular mechanisms underlying pyroptosis, and systematically summarizes the emerging evidence supporting pyroptosis as an immunogenic form of cell death that enhances immune checkpoint blockade efficacy and offers promising prospects for combination cancer therapies.</p>

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The molecular mechanisms of pyroptosis and its implications in tumor immunotherapy

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年1月28日

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  • Guangrui Chen,
  • Zhengjun Zhang,
  • Wei Chong,
  • Gongzheng Qiu,
  • Zecheng Li,
  • Shilong Yang,
  • Xiaoyang Pan,
  • Tingbo Ma,
  • Guodong Lian,
  • Xinying Wang,
  • Leping Li,
  • Feng Tian,
  • Changqing Jing

摘要

Pyroptosis is a form of programmed cell death driven by inflammatory caspases (caspase-1/4/5/11). Distinct from apoptosis, pyroptosis is characterized by the formation of membrane pores, cell swelling followed by rupture, and the release of cellular contents, along with the secretion of a wide range of pro-inflammatory cytokines. Pyroptosis can be activated through two primary pathways: the canonical pathway (caspase-1-dependent) and the non-canonical pathway (caspase-4/5/11-dependent). In recent years, the role of pyroptosis in tumor initiation, progression, and therapy has drawn significant attention, revealing its dual regulatory effects—both anti-tumor and tumor-promoting—highlighting its potential as a novel therapeutic target. Given its pivotal role in modulating anti-tumor immunity, the induction of pyroptosis emerges as a promising strategy to enhance the effectiveness of immunotherapy. To date, an increasing number of studies have explored the synergistic potential of combining pyroptosis-inducing strategies with immunotherapy, particularly immune checkpoint blockade, in cancer treatment.This review explores the molecular mechanisms underlying pyroptosis, and systematically summarizes the emerging evidence supporting pyroptosis as an immunogenic form of cell death that enhances immune checkpoint blockade efficacy and offers promising prospects for combination cancer therapies.