Possible association of decreased NKG2D expression levels and suppression             of the activity of natural killer cells in patients with colorectal cancer.
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.
Department of Clinical Laboratory, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, PR China.
Yajuan
Y
Shen
Chao
C
Lu
Wenjun
W
Tian
Laicheng
L
Wang
Bin
B
Cui
Yulian
Y
Jiao
Chunyan
C
Ma
Ying
Y
Ju
Ling
L
Zhu
Chunhong
C
Shao
Xinqi
X
Liu
Jian
J
Wang
Bingchang
B
Zhang
Zhiming
Z
Lu
D016022:Case-Control Studies; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000276:immunology* / Q000378:metabolism; D005260:Female; D019073:HT29 Cells; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000096:biosynthesis / Q000172:deficiency* / Q000276:immunology
D055655:NK Cell Lectin-Like Receptor Subfamily K