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GSDMD is required for effector CD8+ T cell responses to lung cancer cells

Guangmin Xi1, Jianwei Gao2, Bing Wan2

  • 1Department of Respiratory Medicine, Jinling Hospital, Nanjing University School of Medicine, Nanjing 210002, China; College of Life Science, Qi Lu Normal University, Jinan, Shandong 250012, China.

International Immunopharmacology
|July 6, 2019
PubMed

Insights

Gasdermin D (GSDMD) plays a crucial role in cytotoxic T lymphocyte (CTL) responses against cancer. This study reveals GSDMD is essential for optimal CTL function and cancer cell killing.

Area of Science:

  • Immunology
  • Cell Biology
  • Cancer Research

Background:

  • Gasdermin D (GSDMD) is known as a pyroptosis executioner in monocytes.
  • Its function in other biological systems, particularly T cells, remains largely uncharacterized.

Purpose of the Study:

  • To investigate the role of GSDMD in CD8+ T cells and their cytotoxic functions.
  • To determine if GSDMD is involved in the anti-cancer immune response.

Main Methods:

  • Analysis of GSDMD expression correlation with CD8+ T cell markers in The Cancer Genome Atlas (TCGA) data.
  • Assessment of GSDMD cleavage in activated human CD8+ T cells and OT-1 cytotoxic T lymphocytes (CTLs).
  • Microscopic examination of GSDMD and granzyme B colocalization at immune synapses and evaluation of cytolytic capacity in GSDMD-deficient CD8+ T cells.

Main Results:

  • GSDMD expression positively correlated with CD8+ T cell markers in TCGA cohorts.
  • GSDMD cleavage was elevated in activated CD8+ T cells and CTLs.
  • GSDMD was found near immune synapses, and its deficiency impaired CD8+ T cell killing ability.

Conclusions:

  • This study uncovers a novel function for GSDMD in cytotoxic T lymphocytes.
  • GSDMD is demonstrated to be a critical component for effective CTL-mediated cancer cell killing.
Keywords:
CTLGSDMDGasdermin familyImmune responseNSCLC

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