Combination of intratumoral invariant natural killer T cells and interferon-gamma is associated with prognosis of hepatocellular carcinoma after curative resection

PLoS One. 2013 Aug 5;8(8):e70345. doi: 10.1371/journal.pone.0070345. Print 2013.

Abstract

Purpose: To investigate the prognostic value of intratumoral invariant natural killer T (iNKT) cells and interferon-gamma (IFN-γ) in hepatocellular carcinoma (HCC) after curative resection.

Experimental design: Expression of TRAV10, encoding the Vα24 domain of iNKT cells, and IFN-γ mRNA were assessed by quantitative real-time polymerase chain reaction in tumor from 224 HCC patients undergoing curative resection. The prognostic value of these two and other clinicopathologic factors was evaluated.

Results: Either intratumoral iNKT cells and IFN-γ alone or their combination was an independent prognostic factor for OS (P = 0.001) and RFS (P = 0.001) by multivariate Cox proportional hazards analysis. Patients with concurrent low levels of iNKT cells and IFN-γ had a hazard ratio (HR) of 2.784 for OS and 2.673 for RFS. The areas under the curve of iNKT cells, IFN-γand their combination were 0.618 vs 0.608 vs 0.654 for death and 0.591 vs 0.604 vs 0.633 for recurrence respectively by receiver operating characteristic curve analysis. The prognosis was the worst for HCC patients with concurrent low levels of iNKT cells and IFN-γ, which might be related with more advanced pTNM stage and more vascular invasion.

Conclusions: Combination of intratumoral iNKT cells and IFN-γ is a promising independent predictor for recurrence and survival in HCC, which has a better power to predict HCC patients' outcome compared with intratumoral iNKT cells or IFN-γ alone.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Hepatocellular / diagnosis*
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / pathology*
  • Carcinoma, Hepatocellular / surgery
  • Humans
  • Interferon-gamma / genetics
  • Interferon-gamma / metabolism*
  • Liver Neoplasms / diagnosis*
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / pathology*
  • Liver Neoplasms / surgery
  • Natural Killer T-Cells / immunology
  • Natural Killer T-Cells / metabolism
  • Natural Killer T-Cells / physiology*
  • Prognosis
  • Prospective Studies

Substances

  • Interferon-gamma

Grants and funding

Supported by grants from the National Key Sci-Tech Special Project of China (No. 2012ZX10002010-001/002, 2012ZX10002011-002, 2012ZX10002013-005 and 2012ZX10002-016), the Major Program of the National Nature Science Foundation of China (No. 81030038), and the National Natural Science Foundation of China (No. 81141087 and 81071707). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.