Cancer Immunology, Immunotherapy

, Volume 53, Issue 1, pp 41–52

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

  • Zane C. Neal
  • Michael Imboden
  • Alexander L. Rakhmilevich
  • Kyung-Mann Kim
  • Jacquelyn A. Hank
  • Jean Surfus
  • John R. Dixon
  • Holger N. Lode
  • Ralph A. Reisfeld
  • Stephen D. Gillies
  • Paul M. Sondel
Original Article

DOI: 10.1007/s00262-003-0435-2

Cite this article as:
Neal, Z.C., Imboden, M., Rakhmilevich, A.L. et al. Cancer Immunol Immunother (2004) 53: 41. doi:10.1007/s00262-003-0435-2

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.

Keywords

Tumor escape Hu14.18-IL2 Flt3-ligand Major histocompatibility complex GD2-disialoganglioside 

Abbreviations

ADCC

antibody-dependent cellular cytotoxicity

Flt3-L

Flt3-ligand

GD2

GD2-disialoganglioside

IC

immunocytokine

mAb

monoclonal antibody

NB

neuroblastoma

NXS2

transplantable murine neuroblastoma

s.c.

subcutaneous

Copyright information

© Springer-Verlag 2003

Authors and Affiliations

  • Zane C. Neal
    • 1
  • Michael Imboden
    • 1
  • Alexander L. Rakhmilevich
    • 1
  • Kyung-Mann Kim
    • 1
  • Jacquelyn A. Hank
    • 1
  • Jean Surfus
    • 1
  • John R. Dixon
    • 1
  • Holger N. Lode
    • 2
  • Ralph A. Reisfeld
    • 2
  • Stephen D. Gillies
    • 3
  • Paul M. Sondel
    • 1
  1. 1.University of Wisconsin Comprehensive Cancer CenterUniversity of Wisconsin-MadisonMadisonUSA
  2. 2.Department of ImmunologyScripps Research InstituteLa JollaUSA
  3. 3.EMD-Lexigen Research CentersBillericaUSA

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