NXS2 murine neuroblastomas express increased levels of MHC class I antigens upon recurrence following NK-dependent immunotherapy

Cancer Immunol Immunother. 2004 Jan;53(1):41-52. doi: 10.1007/s00262-003-0435-2. Epub 2003 Sep 18.


We evaluated recurrent NXS2 neuroblastoma tumors that developed following NK- or T-cell-mediated immunotherapy in tumor-bearing mice. Recurrent tumors developed following an NK-dependent antitumor response using a suboptimal dose of hu14.18-IL2, a humanized IL-2 immunocytokine targeted to the GD(2)-ganglioside. This treatment initially induced complete resolution of measurable tumor in the majority of mice, followed, however, by delayed tumor recurrence in some mice. These recurrent NXS2 tumors revealed markedly enhanced (> fivefold) MHC class I antigen expression when compared with NXS2 tumors growing in PBS-treated control mice. A similar level of enhanced MHC class I antigen-expression could be induced on NXS2 cells in vitro by culturing with interferon gamma, and was associated with reduced susceptibility to both NK-cell-mediated tumor cell lysis and antibody-dependent cellular cytotoxicity in vitro. In contrast, Flt3-ligand treatment of NXS2-bearing mice induced a protective T-cell-dependent antitumor memory response. Recurrent NXS2 tumors that developed following Flt3-L therapy revealed a decreased expression of MHC class I antigens. While NXS2 tumors are susceptible to in vivo destruction following either hu14.18-IL2 or Flt3-ligand immunotherapies, these results suggest that some tumor cells may be selected to survive and progress by expressing either higher or lower levels of MHC class I antigen in order to resist either NK- or T-cell-mediated antitumor responses, respectively.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Coculture Techniques
  • Female
  • Histocompatibility Antigens Class I / metabolism*
  • Humans
  • Immunotherapy*
  • Injections, Subcutaneous
  • Interleukin-2 / therapeutic use
  • Killer Cells, Natural / immunology
  • Membrane Proteins / therapeutic use
  • Mice
  • Neoplasm Recurrence, Local / immunology
  • Neoplasm Recurrence, Local / therapy*
  • Neuroblastoma / immunology
  • Neuroblastoma / therapy*
  • Skin Neoplasms / immunology
  • Skin Neoplasms / therapy*
  • T-Lymphocytes / immunology
  • Tumor Cells, Cultured
  • Tyrosine 3-Monooxygenase / genetics
  • Tyrosine 3-Monooxygenase / metabolism


  • Histocompatibility Antigens Class I
  • Interleukin-2
  • Membrane Proteins
  • flt3 ligand protein
  • Tyrosine 3-Monooxygenase