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Published on: June 12, 2021

STIM1 and STIM2-mediated Ca(2+) influx regulates antitumour immunity by CD8(+) T cells

Carl Weidinger1, Patrick J Shaw, Stefan Feske

  • 1Department of Pathology and Cancer Institute, New York University School of Medicine, New York, NY, USA.

EMBO Molecular Medicine
|August 8, 2013
PubMed

Insights

Store-operated calcium entry (SOCE) is crucial for CD8(+) T cells to prevent tumor growth. This pathway regulates cytotoxic T lymphocyte (CTL) function, highlighting its importance in anti-tumor immunity.

Area of Science:

  • Immunology
  • Cell Biology
  • Cancer Research

Background:

  • Store-operated calcium entry (SOCE) via CRAC channels regulates immune cell function.
  • Mutations in ORAI1 or STIM1 cause immunodeficiency and increase susceptibility to virus-associated tumors.
  • Calcium signaling is implicated in cytotoxic lymphocyte function, suggesting a role for SOCE in tumor immune surveillance.

Purpose of the Study:

  • To investigate the role of SOCE in CD8(+) T cells in anti-tumor immunity.
  • To determine if SOCE is essential for the control of melanoma and colon carcinoma growth.

Main Methods:

  • Utilized conditional knockout mice lacking STIM1 and STIM2.
  • Assessed SOCE in CD8(+) T cells.
  • Evaluated tumor engraftment and growth in vivo and in vitro.
  • Measured cytotoxic T lymphocyte (CTL) functions including degranulation, Fas ligand expression, and cytokine production (TNF-α, IFN-γ).

Main Results:

  • SOCE in CD8(+) T cells is required to prevent melanoma and colon carcinoma engraftment.
  • SOCE is essential for controlling tumor growth.
  • SOCE regulates in vivo and in vitro CTL cytotoxic function.
  • SOCE controls CTL degranulation, Fas ligand expression, and production of TNF-α and IFN-γ.

Conclusions:

  • SOCE in CD8(+) T cells plays a critical role in anti-tumor immunity.
  • These findings emphasize the significance of SOCE in tumor immune surveillance.
  • The results are relevant to ongoing discussions about CRAC channel inhibition as a cancer therapy strategy.
Keywords:
CTLSOCESTIM1STIM2tumour immunity

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