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Igniting antitumour immunity with cancer cell pyroptosis

Xin Liu1,2, Elena Goldberg1,2, Jonathan C Kagan3

  • 1Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, USA.

Nature Reviews. Cancer
|July 27, 2026
PubMed

Insights

Gasdermins (GSDMs) trigger pyroptosis, a cell death process that can promote anti-tumor immunity. Activating GSDMs in cancer cells can enhance immune responses with manageable side effects.

Area of Science:

  • Immunology
  • Cell Biology
  • Oncology

Background:

  • Gasdermins (GSDMs) are pore-forming proteins central to pyroptosis, a lytic programmed cell death.
  • GSDMD activation by inflammasomes is a canonical pathway, but GSDMs can be activated by other proteases and modifications.
  • Pyroptosis induction in cancer cells shows potential for anti-tumor immunity.

Purpose of the Study:

  • To review the role of pyroptosis in anti-tumor immunity.
  • To compare pyroptosis with other lytic cell death forms.
  • To explore the synergy of cancer cell pyroptosis with current immunotherapies.

Main Methods:

  • Literature review and synthesis of current knowledge on GSDMs and pyroptosis.
  • Analysis of studies involving GSDM activation in cancer cells.
  • Discussion of pyroptosis in relation to other cell death mechanisms.

Main Results:

  • GSDM activation, independent of inflammasomes, occurs in various cell types, including cancer cells.
  • GSDM activation via T cell granzymes, exogenous delivery, or small molecules promotes anti-tumor immunity.
  • Limited pyroptosis in cancer cells can elicit significant immune infiltration and anti-tumor effects with acceptable toxicity.

Conclusions:

  • Pyroptosis is a promising mechanism for enhancing anti-tumor immunity.
  • Targeting cancer cell pyroptosis may synergize with existing immunotherapies for improved cancer treatment.
  • Further research into pyroptosis modulation holds potential for novel cancer therapies.

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