These authors equally contributed to the work.
Monocyte/macrophage-elicited natural killer cell dysfunction in hepatocellular carcinoma is mediated by CD48/2B4 interactions†
Article first published online: 18 JAN 2013
Copyright © 2012 American Association for the Study of Liver Diseases
Volume 57, Issue 3, pages 1107–1116, March 2013
How to Cite
Wu, Y., Kuang, D.-M., Pan, W.-D., Wan, Y.-L., Lao, X.-M., Wang, D., Li, X.-F. and Zheng, L. (2013), Monocyte/macrophage-elicited natural killer cell dysfunction in hepatocellular carcinoma is mediated by CD48/2B4 interactions. Hepatology, 57: 1107–1116. doi: 10.1002/hep.26192
Potential conflict of interest: Nothing to report.
- Issue published online: 28 FEB 2013
- Article first published online: 18 JAN 2013
- Accepted manuscript online: 7 DEC 2012 12:00AM EST
- Manuscript Accepted: 19 SEP 2012
- Manuscript Received: 17 MAY 2012
- National Basic Research Program of China. Grant Numbers: 2010CB529904, 2011CB811305
- National Natural Science Foundation of China. Grant Numbers: 81171982, 81230073, 81172783
- China Postdoctoral Science Foundation. Grant Number: 2012M510209
- Fundamental Research Funds for the Central Universities
Additional Supporting Information may be found in the online version of this article.
|HEP_26192_sm_SuppFig1.tif||1643K||Supporting Information Figure 1. Paraffin-embedded samples were stained with anti-NK-1 Ab. Distribution of NK cells in human normal liver (n = 9), chronic hepatitis liver (n = 7), remote nontumoral liver (stage I and II: n = 74; stage III and IV: n = 21) and intratumoral tissues (stage I and II: n = 178; stage III and IV: n = 78) of HCC. Bar: 150μm.|
|HEP_26192_sm_SuppFig2.tif||609K||Supporting Information Figure 2. Fresh lymphocytes were isolated from paired peripheral blood, nontumoral liver and intratumoral tissues of HCC patients. CD56+CD3− NK cells were set in the lymphocyte region determined by an FSC and SSC dot plot. A representative gating illustration was shown.|
|HEP_26192_sm_SuppFig3.tif||684K||Supporting Information Figure 3. Definition of nontumor, tumor tissue, invading edge, peritumor stroma and intratumoral regions in human HCC.|
|HEP_26192_sm_SuppFig4.tif||71K||Supporting Information Figure 4. Role of 2B4 and CD48 interaction in regulating NK cell function by autologous TSN-treated monocytes/Mϕ. (A-B) Monocytes from healthy PBMC were incubated in medium alone (MO) or with 15% of the culture supernatant from a hepatoma cell line (HepG2; TSN-MO) for 12 hours. After washing, these monocytes were cultured with autologous NK cells for indicated times (n = 5). Percentages of CD69+, Ki67+, IFN-γ+ and TNF-a+ NK cells were determined by FACS. Dotted line: Medium alone, Dash line: MO, Solid line: TSN-MO. (C) Levels of CD48 expression in monocytes (MO) and TSN-treated monocytes (TSN-MO) were determined by FACS (n = 5). (D) Monocytes (MO) and TSN-treated monocytes (TSN-MO) were cultured with autologous NK cells in the presence or absence of 4 μg/mL anti-2B4 Ab, or isotype control Ab (n = 5). IFN-γ+ and TNF-a+ NK cells after 8-day coculture were determined by FACS. Results are expressed as means ± SEM. *P < 0.05; **P < 0.01.|
|HEP_26192_sm_SuppFig5.tif||1116K||Supporting Information Figure 5. Contact between CD68+ cells (red) and NK-1+ cells (green) in peritumoral stroma was analyzed by confocal microscopy. DAPI, blue. 1 out of 10 representative micrographs was shown.|
|HEP_26192_sm_SuppFig6.tif||674K||Supporting Information Figure 6. Fresh lymphocytes were isolated from paired nontumoral liver and intratumoral tissues of HCC patients (n = 5). Levels of NKG2D and NKp30 expression in NK cells were analyzed by FACS. Results are expressed as means ± SEM.|
|HEP_26192_sm_SuppTables.doc||59K||Supporting Information Tables.|
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