Possible association of decreased NKG2D expression levels and suppression of the activity of natural killer cells in patients with colorectal cancer

Shen,Yajuan; Lu,Chao; Tian,Wenjun; Wang,Laicheng; Cui,Bin; Jiao,Yulian; Ma,Chunyan; Ju,Ying; Zhu,Ling; Shao,Chunhong; Liu,Xinqi; Wang,Jian; Zhang,Bingchang; Lu,Zhiming

doi:10.3892/ijo.2011.1315

Possible association of decreased NKG2D expression levels and suppression of the activity of natural killer cells in patients with colorectal cancer

Authors:
- Yajuan Shen
- Chao Lu
- Wenjun Tian
- Laicheng Wang
- Bin Cui
- Yulian Jiao
- Chunyan Ma
- Ying Ju
- Ling Zhu
- Chunhong Shao
- Xinqi Liu
- Jian Wang
- Bingchang Zhang
- Zhiming Lu
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Affiliations: Department of Clinical Laboratory, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, P.R. China
Published online on: December 22, 2011 https://doi.org/10.3892/ijo.2011.1315
Pages: 1285-1290

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Abstract

Natural-killer group 2 (NKG2), a natural killer (NK) cell receptor, plays a critical role in regulating NK cytotoxicity. In this study, we investigated the expression levels of natural killer group 2 member A (NKG2A) and natural killer group 2 member D (NKG2D) in NK cells as well as the regulatory function of NKG2D in patients with colorectal cancer (CRC). Sixty-two CRC patients and 32 healthy controls were enrolled in this study. The expression levels of NKG2A and NKG2D mRNA in peripheral blood mononuclear cells (PBMCs) were investigated using real-time PCR. Flow cytometry was performed to assay the levels of NKG2A and NKG2D proteins in NK cells. The levels of NKG2D mRNA in PBMCs in the patients were significantly lower than those in the controls [mean ± SD, 1.11±0.60 (CRC patients) vs. 1.65±0.71 (healthy controls); p<0.01], whereas the 2 groups showed no apparent difference in the levels of NKG2A mRNA (p>0.05). In addition, the patients showed significantly lower NKG2D levels in NK cells than the controls did (71.23%±8.31% [CRC patients] vs. 79.39%±5.58% [healthy controls]; p<0.01). However, we observed no distinct difference in the NKG2A expression levels in NK cells between the 2 groups (p>0.05). Notably, blockage of NKG2D signaling with anti-NKG2D antibodies ex vivo resulted in decreased cytotoxicity and CD107a degranulation. Our data revealed that the decrease in NKG2D expression levels may have been associated with suppression of NK cell activity in CRC patients.

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