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Molecular mechanisms and functions of pyroptosis in inflammation and antitumor immunity

Junwei Hou1, Jung-Mao Hsu2, Mien-Chie Hung3

  • 1Xiangya Cancer Center, Xiangya Hospital, Central South University, Xiangya Road 87, Changsha 410008, Hunan, China; Otolaryngology Major Disease Research Key Laboratory of Hunan Province, Xiangya Road 87, Changsha 410008, Hunan, China; Department of Otolaryngology Head and Neck Surgery, Xiangya Hospital, Central South University, Xiangya Road 87, Changsha 410008, Hunan, China; Department of Molecular and Cellular Oncology, the University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Molecular Cell
|September 25, 2021
PubMed

Insights

Immune cell pyroptosis (ICP) and cancer cell pyroptosis (CCP) utilize different gasdermins and caspases. While ICP involves GSDMD, CCP uses GSDMB, GSDMC, or GSDME, impacting antitumor immunity differently.

Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Mechanisms

Background:

  • Gasdermin D (GSDMD) cleavage by caspase-1 initiates immune cell pyroptosis (ICP) for pathogen defense.
  • Cancer cell pyroptosis (CCP) involves distinct mechanisms, utilizing GSDMB, GSDMC, or GSDME as executioners.

Purpose of the Study:

  • To elucidate the distinct molecular mechanisms underlying ICP and CCP.
  • To analyze the differential roles of ICP and CCP in inflammation and antitumor immunity.
  • To identify actionable therapeutic targets based on pyroptosis pathways.

Main Methods:

  • Comparative analysis of gasdermin family members (GSDMD, GSDMB, GSDMC, GSDME) in pyroptosis.
  • Investigation of caspase and granzyme involvement in CCP induction.
  • Assessment of inflammatory and antitumor immune responses elicited by ICP and CCP.

Main Results:

  • CCP is triggered by apoptotic caspases and granzymes, distinct from the inflammatory caspases activating ICP.
  • Accumulation of protease-cleaved gasdermin proteins is essential for CCP.
  • ICP and CCP induce inflammation with opposing effects on antitumor immunity and therapeutic outcomes.

Conclusions:

  • ICP and CCP represent distinct cellular death pathways with divergent impacts on antitumor immunity.
  • Understanding these differences offers novel therapeutic strategies targeting pyroptosis in cancer and infection.
Keywords:
Antitumor immunityCancer cell pyroptosisGasderminImmune cell pyroptosisInflammationPyroptosis

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