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Increased blood spermine levels decrease the cytotoxic activity of lymphokine-activated killer cells: a novel mechanism of cancer evasion

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Abstract

Increased blood polyamine levels, often observed in cancer patients, have negative impacts on patient prognosis and are associated with tumor progression. The purpose of our study was to examine the effects of polyamines on cellular immune function. Peripheral blood mononuclear cells (PBMCs) from healthy volunteers were cultured with the human natural polyamines spermine, spermidine, or putrescine, and the effects on immune cell function were examined. The correlation between post-operative changes in blood polyamine levels and lymphokine-activated killer (LAK) activity was also examined in cancer patients. Spermine decreased the adhesion of non-stimulated PBMCs to tissue culture plastic in a dose- and a time-dependent manner without affecting cell viability or activity. This decrease in adhesion capacity was accompanied by a decrease in the number of CD11a bright-positive and CD56 bright-positive cells. Upon stimulation with interleukin 2 to activate LAK cytotoxicity, PBMCs cultured overnight with 100 or 500 μM spermine showed decreased cytotoxic activity against Daudi cells (91.5 ± 1.7 and 84.9 ± 3.0%, respectively (n = 6) compared to PBMC cultured without polyamines). In a group of 25 cancer patients, changes in blood spermine levels after surgery were negatively correlated with changes in LAK cytotoxicity after surgery (r = −0.510, P = 0.008: n = 25). Increased blood spermine levels may be an important factor in the suppression of anti-tumor immune cell function.

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Abbreviations

PBMCs:

Peripheral blood mononuclear cells

TNF:

Tumor necrosis factor

RBC:

Red blood cell

LAK:

Lymphokine activated killer

LFA-1:

Leukocyte function-associated antigen-1

HPLC:

High performance liquid chromatography

FITC:

Fluorescein isothiocyanate

PE:

Phycoerythrin

ICAMs:

Intercellular adhesion molecules

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Authors and Affiliations

  1. Department of Surgery, Omiya Medical Center, Jichi Medical University, 1-847 Amanuma, Omiya, Saitama City, Saitama, 330-0834, Japan

    Yoshihiko Kano, Kuniyasu Soda, Takeshi Nakamura, Masaaki Saitoh & Fumio Konishi

  2. First Department of Integrated Medicine, Omiya Medical Center, Jichi Medical University, 1-847 Amanuma, Omiya, Saitama City, Saitama, 330-0834, Japan

    Masanobu Kawakami

Authors
  1. Yoshihiko Kano
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  2. Kuniyasu Soda
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  3. Takeshi Nakamura
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  4. Masaaki Saitoh
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  5. Masanobu Kawakami
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  6. Fumio Konishi
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Correspondence to Kuniyasu Soda.

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Kano, Y., Soda, K., Nakamura, T. et al. Increased blood spermine levels decrease the cytotoxic activity of lymphokine-activated killer cells: a novel mechanism of cancer evasion. Cancer Immunol Immunother 56, 771–781 (2007). https://doi.org/10.1007/s00262-006-0229-4

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  • DOI: https://doi.org/10.1007/s00262-006-0229-4

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