Cytostatic and tumoricidal activities of tumor necrosis factor-treated neutrophils

H Shau1

  • 1Division of Surgical Oncology, UCLA Medical Center 90024.

Immunology Letters
|January 1, 1988
PubMed

Insights

Tumor necrosis factor (TNF) activates polymorphonuclear neutrophils (PMN) to inhibit tumor cell growth. Hydrogen peroxide produced by TNF-activated PMN is key to this tumor cell cytostasis.

Area of Science:

  • Immunology
  • Cell Biology
  • Oncology

Background:

  • Tumor necrosis factor (TNF) is a key cytokine in inflammation and immunity.
  • Polymorphonuclear neutrophils (PMN) are critical immune cells involved in host defense against pathogens and tumors.

Purpose of the Study:

  • To investigate the role of TNF-activated PMN in tumor cell cytostasis and cytotoxicity.
  • To elucidate the mechanisms underlying TNF-induced PMN anti-tumor activity.

Main Methods:

  • Incubation of three tumor cell lines with recombinant human TNF and PMN.
  • Dose-response experiments with PMN and TNF.
  • Neutralization studies using anti-TNF antibodies.
  • Enzymatic assays with catalase and superoxide dismutase (SOD).

Main Results:

  • PMN incubated with TNF exhibited significant dose-dependent cytostasis against all tested tumor cell lines.
  • TNF-induced PMN cytostasis was neutralized by anti-TNF antibodies.
  • Catalase, but not SOD, abrogated the cytostatic effect, indicating hydrogen peroxide involvement.
  • TNF-treated PMN demonstrated cytotoxicity, with significant lysis observed after prolonged incubation (>24 h).

Conclusions:

  • TNF-activated PMN possess potent anti-tumor cytostatic properties.
  • Hydrogen peroxide is a critical mediator of TNF-induced PMN-mediated tumor cell cytostasis.
  • TNF-activated PMN can also induce tumor cell cytotoxicity, though this effect requires extended incubation periods.

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