Lack of class II transactivator causes severe deficiency of HLA-DR expression in small cell lung cancer

J Pathol. 1999 Jan;187(2):191-9. doi: 10.1002/(SICI)1096-9896(199901)187:2<191::AID-PATH206>3.0.CO;2-3.


Small cell lung cancer (SCLC) is characteristically not associated with tumour-infiltrating lymphocytes. Since SCLC has been reported to show marked reduction of class I HLA, the reduced expression has been considered a means of escaping anti-cancer immunity. However, HLA-DR expressed in cancer cells is now known to contribute to anti-cancer immunity. To clarify the difference in HLA-DR expression between SCLC and non-small cell lung cancer (NSCLC), and the mechanism, the expression and the cis- and trans-acting factors involved were investigated. HLA-DR was not immunohistochemically detected in any SCLC and could not be induced by interferon gamma (IFN-gamma) in any SCLC cell line, whereas HLA-DR was expressed to varying degrees and was easily induced in NSCLC. SCLC cell lines lacked class II transactivator (CIITA) even after IFN-gamma induction, whereas NSCLC cell lines expressed CIITA. The other class II HLA-specific transcription factors were expressed and genomic DNA of HLA-DR, including the promoter, was conserved well both in SCLC and in NSCLC cell lines. CIITA transfection improved the expression of HLA-DR in SCLC. In conclusion, the lack of CIITA results in severe deficiency of HLA-DR expression in SCLC. Since CIITA has also been reported to induce class I HLA, CIITA transfection might make it possible to establish effective anti-cancer immunotherapy against SCLC through the up-regulation of class I and class II HLA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Northern
  • Blotting, Southern
  • Carcinoma, Non-Small-Cell Lung / immunology
  • Carcinoma, Small Cell / genetics
  • Carcinoma, Small Cell / immunology*
  • Gene Expression
  • HLA-DR Antigens / genetics
  • HLA-DR Antigens / metabolism*
  • Humans
  • Interferon-gamma / immunology
  • Lung Neoplasms / genetics
  • Lung Neoplasms / immunology*
  • Nuclear Proteins*
  • RNA, Messenger / genetics
  • Recombinant Proteins
  • Trans-Activators / deficiency*
  • Trans-Activators / genetics
  • Transfection
  • Tumor Cells, Cultured


  • HLA-DR Antigens
  • MHC class II transactivator protein
  • Nuclear Proteins
  • RNA, Messenger
  • Recombinant Proteins
  • Trans-Activators
  • Interferon-gamma