Crosstalk between hypoxia-induced pyroptosis and immune escape in cancer: From mechanisms to therapy

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Seyed Mohammadmahdi Meybodi1, Mahsa Ejlalidiz2, Mohammadsadegh Rezaeian Manshadi3

  • 1Young Researchers and Elite Club, Tabriz Branch, Islamic Azad University, Tabriz, Iran.

Critical Reviews in Oncology/Hematology
|April 3, 2024
PubMed

Insights

Pyroptosis, a form of programmed cell death, has a complex role in cancer. Targeting the interplay between tumor hypoxia, pyroptosis, and immune escape offers a promising therapeutic strategy.

Area of Science:

  • Immunology
  • Cell Biology
  • Oncology

Background:

  • Pyroptosis, involving gasdermin (GSDM) cleavage, is activated via canonical and non-canonical inflammasome pathways.
  • The role of pyroptosis in cancer is context-dependent, varying with tumor type, stage, location, and immune status.
  • Neither acute nor chronic pyroptosis can be definitively classified as solely tumor-promoting or inhibiting.

Purpose of the Study:

  • To review the intricate relationship between pyroptosis and cancer.
  • To highlight the crosstalk between tumor hypoxia, pyroptosis, and immune evasion.
  • To explore the potential of targeting the hypoxia-pyroptosis-immune escape axis for cancer therapy.

Main Methods:

  • Literature review of pyroptosis mechanisms and cancer biology.
  • Analysis of the role of hypoxia-inducible factor (HIF) signaling.
  • Examination of immune checkpoint regulation in the tumor microenvironment (TME).

Main Results:

  • Pyroptosis's impact on tumors is nuanced, influencing cancer progression and anti-tumor immunity.
  • Chronic pyroptosis may promote tumor growth, while acute pyroptosis can enhance anti-cancer immunity.
  • Tumor hypoxia, via HIF signaling, modulates pyroptosis and immune checkpoint expression.

Conclusions:

  • The interplay between hypoxia, pyroptosis, and immune evasion in the TME is complex.
  • Targeting the hypoxia-pyroptosis-immune escape axis presents a potential therapeutic avenue.
  • Further research into this axis may lead to novel cancer treatment strategies.
Keywords:
Anti-cancer immunityGasdermin pathwaysHypoxia signalingImmune checkpoint blockadeProgrammed cell deathPyroptosisTumor microenvironment

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