Peng Yun-Peng, Zhu Yi, Zhang Jing-Jing, Xu Ze-Kuan, Qian Zhu-Yin, Dai Cun-Cai, Jiang Kui-Rong, Wu Jun-Li, Gao Wen-Tao, Li Qiang, Du Qing, Miao Yi
Department of General Surgery, The first Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing 210029, People's Republic of China.
J Transl Med. 2013 Oct 20;11:262. doi: 10.1186/1479-5876-11-262.
Digestive malignancies, especially pancreatic cancer (PC), gastric cancer (GC), and colorectal cancer (CRC), still occur at persistently high rates, and disease progression in these cancers has been associated with tumor immunosurveillance escape. Natural killer (NK) cell dysfunction may be responsible for this phenomenon, however, the exact relationship between tumor immunosurveillance escape in digestive malignancies and NK cell dysfunction remains unclear.
Percentage of the surface receptors NKG2A, KIR3DL1, NKG2D, NKp30, NKp44, NKp46, and DNAM-1, as well as the cytotoxic granules perforin and granzyme B positive NK cells were determined in patients with pancreatic cancer (n=31), gastric cancer (n=31), and CRC (n=32) prior to surgery and healthy controls (n=31) by multicolor flow cytometry. Independent t-tests or Mann-Whitney U-tests were used to compare the differences between the patient and healthy control groups, as well as the differences between patients with different pathologic features of cancer.
Percentage of NKG2D, NKp30, NKp46, and perforin positive NK cells was significantly down-regulated in patients with PC compared to healthy controls, as well as GC and CRC; reduced levels of these molecules was associated with indicators of disease progression in each malignancy (such as histological grade, depth of invasion, lymph node metastasis). On the contrary, percentage of KIR3DL1 positive NK cells was significantly increased in patients with PC, as well as GC and CRC, but was not associated with any indicators of disease progression.
Altered percentage of surface receptors and cytotoxic granules positive NK cells may play a vital role in tumor immunosurveillance escape by inducing NK cell dysfunction in patients with PC, GC, and CRC.
消化系统恶性肿瘤，尤其是胰腺癌（PC）、胃癌（GC）和结直肠癌（CRC）的发病率仍然居高不下，这些癌症的疾病进展与肿瘤免疫监视逃逸有关。自然杀伤（NK）细胞功能障碍可能是导致这一现象的原因，然而，消化系统恶性肿瘤的肿瘤免疫监视逃逸与NK细胞功能障碍之间的确切关系仍不清楚。
采用多色流式细胞术检测胰腺癌患者（n = 31）、胃癌患者（n = 31）和结直肠癌患者（n = 32）术前及健康对照者（n = 31）表面受体NKG2A、KIR3DL1、NKG2D、NKp30、NKp44、NKp46和DNAM-1的百分比，以及细胞毒性颗粒穿孔素和颗粒酶B阳性NK细胞的百分比。采用独立样本t检验或曼-惠特尼U检验比较患者组与健康对照组之间的差异，以及不同病理特征癌症患者之间的差异。
与健康对照组以及胃癌和结直肠癌患者相比，胰腺癌患者中NKG2D、NKp30、NKp46和穿孔素阳性NK细胞的百分比显著下调；这些分子水平的降低与每种恶性肿瘤的疾病进展指标（如组织学分级、浸润深度、淋巴结转移）相关。相反，胰腺癌、胃癌和结直肠癌患者中KIR3DL1阳性NK细胞的百分比显著增加，但与任何疾病进展指标均无关。
表面受体和细胞毒性颗粒阳性NK细胞百分比的改变可能通过诱导胰腺癌、胃癌和结直肠癌患者的NK细胞功能障碍，在肿瘤免疫监视逃逸中发挥重要作用。
