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Related Experiment Videos

Histamine and cytokine therapy

K Hellstrand1, S Hermodsson, P Naredi

  • 1Department of Virology, University of Göteborg, Sweden.

Acta Oncologica (Stockholm, Sweden)
|September 22, 1998
PubMed
Summary

Histamine enhances cancer immunotherapy by blocking tumor-associated macrophages. This approach, combining histamine with Interleukin-2 (IL-2) and Interferon-alpha (IFN-alpha), shows promise in treating melanoma and acute myelogenous leukemia (AML).

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Area of Science:

  • Immunology
  • Cancer Biology
  • Pharmacology

Background:

  • Interleukin-2 (IL-2) and Interferon-alpha (IFN-alpha) activate anti-tumor immune cells but often yield disappointing clinical results.
  • Intratumoral monocytes/macrophages (MO) can inhibit cytokine-induced anti-tumor immune responses, partly via reactive oxygen species (ROS) production.
  • ROS from MO potently suppress natural killer (NK) cell functions, including tumor cell cytotoxicity.

Purpose of the Study:

  • To investigate whether histamine can overcome MO-mediated inhibition of anti-tumor immunity.
  • To evaluate the synergistic effects of histamine with IL-2 and/or IFN-alpha on anti-tumor effector cells.
  • To assess the clinical efficacy of histamine combined with cytokine immunotherapy in cancer patients.

Main Methods:

Related Experiment Videos

  • In vitro studies assessing histamine's effect on MO-derived ROS and NK-cell cytotoxicity.
  • In vivo studies in tumor-bearing mice to evaluate histamine potentiation of cytokine therapy.
  • Pilot clinical trials in metastatic melanoma and acute myelogenous leukemia (AML) patients receiving histamine with IL-2/IFN-alpha.

    • Main Results:

    • Histamine inhibits ROS formation in MO, synergizing with IL-2 and IFN-alpha to enhance NK-cell mediated tumor cell killing in vitro.
    • Histamine treatment potentiated cytokine-induced anti-tumor activity in tumor-bearing mice.
    • Pilot trials suggest histamine addition to IL-2/IFN-alpha prolongs survival and induces regression in refractory melanoma and protects AML patients from relapse.

    Conclusions:

    • Histamine can reverse immunosuppression mediated by tumor-associated macrophages.
    • Combining histamine with IL-2 and/or IFN-alpha represents a promising strategy for cancer immunotherapy.
    • Randomized trials are warranted to confirm the therapeutic benefits of histamine in melanoma and AML.