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Updated: Aug 19, 2026

Isolation and Characterization of Neutrophils with Anti-Tumor Properties
Published on: June 19, 2015
Characteristics and mechanism of neutrophil-mediated cytostasis induced by tumor necrosis factor
1Division of Surgical Oncology, UCLA Medical Center, Los Angeles, CA 90024.
Abstract:
After being treated with rTNF, polymorphonuclear neutrophils (PMN) were highly suppressive to the growth of four different tumor target cells, Raji, K562, UCLA-SO-M14, and U937. Neutralizing TNF with specific antibodies before PMN were treated blocked induction of the anti-proliferative activity against Raji. However, after PMN were exposed to TNF the cytostatic activity could not be reversed by the antibody or by washing off TNF, indicating that the continuous presence of TNF was not required for expression of the anti-proliferative function. Addition of the hydrogen peroxide (HP) scavenger, catalase, at the beginning of the assay inhibited the cytostatic activity, suggesting that HP was involved in suppressing the tumor cell growth. In contrast, other reactive oxygen species inhibitors such as superoxide dismutase, sodium azide, L-methionine, or deferoxamine did not inhibit the cytostasis. HP alone at above 10 microM was cytostatic to Raji cells. The presence of TNF did not increase the sensitivity of Raji to HP. TNF activated PMN to produce HP but the amount of HP released in the culture supernatant was too low for direct cytostasis. PMN also became more adherent after TNF treatment. Therefore, the TNF-induced cytostasis may be mediated by local high concentrations of HP produced by PMN.
Insights
Tumor cell growth is suppressed by polymorphonuclear neutrophils (PMN) activated by tumor necrosis factor (TNF). This TNF-induced suppression is mediated by hydrogen peroxide (HP) produced by PMN, not by TNF itself.
Area of Science:
- Immunology
- Cell Biology
- Biochemistry
Background:
- Tumor necrosis factor (TNF) plays a crucial role in immune responses and inflammation.
- Polymorphonuclear neutrophils (PMN) are key immune cells involved in host defense.
- The anti-tumor activity of PMN is an area of active research.
Purpose of the Study:
- To investigate the mechanism by which TNF-activated PMN suppress tumor cell growth.
- To determine the role of reactive oxygen species (ROS), specifically hydrogen peroxide (HP), in this suppressive activity.
- To elucidate the signaling pathway involved in TNF-induced PMN anti-proliferative function.
Main Methods:
- Treatment of PMN with recombinant TNF (rTNF) and subsequent co-culture with tumor cell lines (Raji, K562, UCLA-SO-M14, U937).
- Use of neutralizing antibodies against TNF and scavengers for reactive oxygen species (catalase, superoxide dismutase) to assess the role of TNF and HP.
- Measurement of HP production by PMN and assessment of HP's direct cytostatic effect on tumor cells.
Main Results:
- TNF-activated PMN exhibited significant suppressive activity against four different tumor cell lines.
- Neutralization of TNF before PMN activation blocked the anti-proliferative effect.
- The suppressive activity was dependent on hydrogen peroxide (HP) production by PMN, as indicated by inhibition with catalase.
- Continuous presence of TNF was not required for the anti-proliferative function after PMN activation.
- HP alone demonstrated cytostatic effects on Raji cells, but TNF did not enhance Raji cell sensitivity to HP.
Conclusions:
- TNF-activated PMN induce cytostasis in tumor cells through a mechanism involving hydrogen peroxide (HP).
- The anti-proliferative effect is mediated by locally high concentrations of HP produced by PMN, rather than by direct action of TNF.
- These findings highlight a novel mechanism of anti-tumor activity involving PMN and HP, with potential therapeutic implications.
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