Tumor Biology

, Volume 37, Issue 8, pp 11187–11198 | Cite as

Co-expression of ILT4/HLA-G in human non-small cell lung cancer correlates with poor prognosis and ILT4-HLA-G interaction activates ERK signaling

  • Yanwen Zhang
  • Jianqiang Zhao
  • Lijun Qiu
  • Pei Zhang
  • Juan Li
  • Dong Yang
  • Xiaojuan Wei
  • Yali Han
  • Siyue Nie
  • Yuping Sun
Original Article


Non-small cell lung cancer (NSCLC) is the most common malignant tumor in the world, of which prognosis is generally poor due to insufficient mechanistic understanding. To explore the molecular pathogenesis of NSCLC, the co-expression of immunoglobulin-like transcript 4 (ILT4) and its ligand human leukocyte antigen G (HLA-G) in NSCLC tissues and cells were investigated. Here, we detected the expression of ILT4 and HLA-G in 81 tumor specimens from primary NSCLC patients, and we found that co-expression of ILT4/HLA-G was significantly associated with regional lymph node involvement, advanced stages, and the overall survival of patients. In NSCLC cell lines, HLA-G expression increased/decreased accordingly when ILT4 was up-/down-regulated, and ILT4 expression increased in a concentration-dependent manner via the stimulation of HLA-G fusion protein. Interestingly, HLA-G fusion protein could also up-regulate the phospho-ERK1/2 expression, which means the activation of extracellular signal-regulated kinase (ERK) signaling. All in all, our results indicate that the ILT4-HLA-G interaction might play an important role in NSCLC progression. Identification of ILT4 and HLA-G expression may provide an indicator to predict prognosis and guide prevention and treatment of NSCLC.


Non-small cell lung cancer Immunoglobulin-like transcript 4 Human leukocyte antigen-G Extracellular signal-regulated kinase 



Non-small cell lung cancer


Immunoglobulin-like transcript 4


Human leukocyte antigen G


Dendritic cells


Major histocompatibility complex class I molecules


Immunoreceptor tyrosine-based inhibitory motifs


Protein tyrosine phosphatase


Vascular endothelial growth factor-C


Angiopoietin-like proteins


PI3K/protein kinase B


Extracellular signal regulated kinases


Nuclear factor


Overall survival


Infiltrating lymphocytes


Paired Ig-like receptor


Human hematopoietic stem cells


Acute myeloid leukemia


Epidermal growth factor receptor



This work was supported by the National Natural Science Foundation of China (Grant No. 81372334), the Department of Science and Technology of Shandong Province (Grant No. 2013GSF12107), and the Department of Science and Technology of Jinan City (Grant No. 201201061). We thank Dong Zhao and Huiping Liu of the Department of Pathology, Jinan Central Hospital, Shandong University, for performing the immunohistochemical assays.

Author contributions

Y.S. conceived and designed the experiments. Y.Z., P.Z., J.L., D.Y., X.W., Y.H., and S.N. performed the experiments. Y.S., Y.Z., J.Z., and L.Q. analyzed data and wrote the manuscript.

Compliance with ethical standards

Conflicts of interest



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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2016

Authors and Affiliations

  • Yanwen Zhang
    • 1
    • 2
  • Jianqiang Zhao
    • 2
  • Lijun Qiu
    • 3
  • Pei Zhang
    • 2
  • Juan Li
    • 2
  • Dong Yang
    • 2
  • Xiaojuan Wei
    • 2
  • Yali Han
    • 2
  • Siyue Nie
    • 2
  • Yuping Sun
    • 2
  1. 1.Department of Oncology, School of MedicineShandong UniversityJinanChina
  2. 2.Department of Oncology, Jinan Central HospitalShandong UniversityJinanChina
  3. 3.Department of Pharmacy, Jinan Central HospitalShandong UniversityJinanChina

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