NK cell exhaustion and NK-based checkpoint blockade immunotherapy / 中国免疫学杂志

As the first line of defense of the host immune system, natural killer cells play important roles in anti-tumor immunity, either by direct anti-tumor effects, or by assisting T cell immune responses. However, NK cells are usually functionally exhausted in tumor microenvironment, accompanied with dysregulated expression of an array of surface receptors, restricting the effector potentials of NK cells. NK-based checkpoint immunotherapy aims to trigger anti-tumor efficacy by blocking NK cell surface inhibitory receptors, unleashing NK cells from inhibitory signals of the tumor microenvironment, and reversing NK cell exhaustion, representing a novel strategy in cancer therapy. With more in-depth research to reveal the mechanisms of action, indications, and biomarkers for specific NK cell checkpoint molecules, we shall fully exploit the potentials of NK-based checkpoint blockade immunotherapy.

Clinical effects of subcutaneous tunnel hepatocholangioplasty on the treatment of hepatolithiasis / 中华外科杂志

<p><b>OBJECTIVE</b>To evaluate the therapeutic effect of subcutaneous tunnel hepaticoplasty on the treatment of hepatolithiasis.</p><p><b>METHODS</b>The early complications and clinical effects of 99 hepatolithiasis cases who underwent subcutaneous tunnel hepaticoplasty from January 1993 to August 2006 were analyzed retrospectively. The stones of 28 (28.3%) patients were in the left lobe, 24.2% (24/99) in the right, and 47.5% (47/99) in bilateral lobe. Sixty-six patients (66.7%) had both stones and biliary strictures. During the procedure, a portion of the liver habouring stone was resected if necessary. The hepatic duct and strictures were opened, the stones were removed, and the porta hepatis was repaired by one end of a segment of jejunum. The other end of the jejunum was set subcutaneously. The gall bladders of 27 patients (27.3%) were used as subcutaneous tunnel instead.</p><p><b>RESULTS</b>Ninety-five out of ninety-nine cases were followed up with an average of 4.2 years (1 month to 13.5 years). The rates of residual stone, recurrent stone and cholangitis were 23.2% (23/99), 20.0% (19/95) and 14.7% (14/95) respectively. Postoperatively, 34 cases who had residual or recurrent stones were underwent lithotomy by choledochoscope through the subcutaneous blind loop and the achievement ratio was 91.2% (31/34).</p><p><b>CONCLUSIONS</b>Subcutaneous tunnel hepatocholangioplasty decreases the relapsing cholangitis effectively, and makes an easy way to take out residual or recurrent stones.</p>

The negative regulatory effect of IFN-gamma on cognitive function of human natural killer cells / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the regulatory effect of IFN-gamma on recognition of target cells by human natural killer (NK) cells.</p><p><b>METHODS</b>The cytotoxic activity of human NK cell lines (NK92, NKL) was detected by MTT method. Expression of NK cell receptors (NKG2D, NKG2A/B, KIR2DL1 and KIR2DS1) and MICA on target cells (the ligand of NKG2D) was measured by RT-PCR.</p><p><b>RESULTS</b>Both NK92 and NKL cells exerted higher cytotoxicity to tumor cells with MICA expression, while tumors without MICA expression could resist NK cell lysis. IFN-gamma (> 1000 U/ml) inhibited NK lysis of tumor cells with MICA expression through down-regulating the expression of NKG2D, but up-regulating the expression of NKG2A/B and KIR2DL1.</p><p><b>CONCLUSION</b>IFN-gamma has a negative effect on activation and cytotoxicity of human NK cells by altering the balance between the expression of activating and inhibitory receptors on NK cells in favor of inhibition. This may serve to limit NK cell over-activation in vivo.</p>

Negative Regulatory Effect of T-Lymphocytes on the Expansion of Human Bone Marrow Hematopoietic Cells In Vitro / 中国实验血液学杂志

In this research, the regulatory effects of T-lymphocytes on the expansion of hematopoietic cells in human bone marrow were studied. Anti-CD3 McAb and anti-CD8 McAb were used to eliminate the T-lymphocytes in bone marrow MNCs. Cell surface antigens were analysed by flow cytometry. Hematopoietic cells expanded with hematopoietic growth factors (HGFs) in a liquid culture system and the number of CD34(+) cell, CFU-GM and CFU-GEMM were determined. After cultured with HGFs for 20 days the total number of cells expanded by 75.8, 79.6, 77.4 and 67.0 folds respectively in three experimental groups (anti-CD3 McAb, anti-CD8 McAb and anti-CD3 + anti-CD8 McAb) and control group (MNC of bone marrow). The number of CFU-GM in the four groups were 173.67 +/- 18.90, 165.33 +/- 26.58, 170.33 +/- 21.50 and 79.67 +/- 8.33 respectively. The number of CFU-GEMM in the four groups were 431.33 +/- 34.56, 370.33 +/- 42.10, 386.67 +/- 10.02 and 177.67 +/- 26.86 respectively. There were significant differences in the number of CFU-GM and CFU-GEMM between experimental groups and control group. The results showed that the T-lymphocytes in bone marrow could inhibit the expansion of hematopoietic cells in vitro and the formation of CFU-GM and CFU-GEMM. The regulatory mechanism was to be explored.