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Related Experiment Videos

Acidic pH inhibits non-MHC-restricted killer cell functions.

B Fischer1, B Müller, K G Fischer

  • 1Institut für Biophysik und Strahlenbiologie, Albert-Ludwigs-Universität Freiburg, Albertstrasse 23, Freiburg i. Br., D-79104, Germany.

Clinical Immunology (Orlando, Fla.)
|August 31, 2000
PubMed
Summary
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Solid tumors create an acidic environment that impairs immune cell function. This study shows acidic pH inhibits key cytotoxic mechanisms, hindering anti-tumor responses and immunotherapy effectiveness.

Area of Science:

  • Immunology
  • Cancer Biology
  • Cellular Physiology

Background:

  • Immunotherapy for advanced solid tumors has limited success.
  • Tumor microenvironments often exhibit acidic interstitial pH.
  • Acidic pH is implicated in tumor cell immune evasion.

Purpose of the Study:

  • Investigate the impact of acidic extracellular pH on immune effector cell functions.
  • Elucidate mechanisms by which acidic pH inhibits anti-tumor cytotoxicity.
  • Assess the effect of pH on various immune cell killing pathways.

Main Methods:

  • Utilized peripheral blood mononuclear cells (PBMC) and IL-2-activated LAK cells as effector cells.
  • Assessed cytotoxic activity against TNFalpha-sensitive/resistant and Fas-positive/negative tumor cells.

Related Experiment Videos

  • Manipulated extracellular pH and calcium levels to analyze killing pathways (perforin/granzymes, TNFalpha, Fas/FasL).
  • Main Results:

    • Declining extracellular pH significantly inhibited perforin/granzyme release, TNFalpha secretion, and Fas/FasL-mediated cytotoxicity.
    • Acidic pH also affected the secretion of IFNgamma, IL-10, and TGF-beta(1).
    • A pH of 5.8 nearly abolished effector cell function by impairing mitochondrial activity and intracellular pH regulation.

    Conclusions:

    • Tumor acidity severely compromises essential immune effector cell functions.
    • Acidic tumor microenvironments contribute to immunosuppression in vivo.
    • Targeting tumor acidity could enhance anti-tumor immunity and immunotherapy efficacy.