NXS2 murine neuroblastomas express increased levels of MHC class I antigens upon recurrence following NK-dependent immunotherapy.
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.
D000818:Animals; D018920:Coculture Techniques; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D006801:Humans; D007167:Immunotherapy; D007279:Injections, Subcutaneous; D007376:Interleukin-2 / Q000627:therapeutic use; D007694:Killer Cells, Natural / Q000276:immunology; D008565:Membrane Proteins / Q000627:therapeutic use; D051379:Mice; D009364:Neoplasm Recurrence, Local / Q000276:immunology / Q000628:therapy*; D009447:Neuroblastoma / Q000276:immunology / Q000628:therapy*; D012878:Skin Neoplasms / Q000276:immunology / Q000628:therapy*; D013601:T-Lymphocytes / Q000276:immunology; D014407:Tumor Cells, Cultured; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics / Q000378:metabolism
D015395:Histocompatibility Antigens Class I; D007376:Interleukin-2; D008565:Membrane Proteins; C084881:flt3 ligand protein; D014446:Tyrosine 3-Monooxygenase