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- Title
NXS2 murine neuroblastomas express increased levels of MHC class I antigens upon recurrence following NK-dependent immunotherapy.
- Authors
Neal, Zane C.; Imboden, Michael; Rakhmilevich, Alexander L.; Kyung-Mann Kim; Hank, Jacquelyn A.; Surfus, Jean; Dixon, John R.; Lode, Holger N.; Reisfeld, Ralph A.; Gillies, Stephen D.; Sondel, Paul M.
- Abstract
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 GD2-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 γ, 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.
- Subjects
NEUROBLASTOMA; ANTIGENS; NERVOUS system tumors; CANCER cells; IMMUNOTHERAPY; SARCOMA
- Publication
Cancer Immunology, Immunotherapy, 2004, Vol 53, Issue 1, p41
- ISSN
0340-7004
- Publication type
Article
- DOI
10.1007/s00262-003-0435-2