Autologous control of a highly malignant syngeneic CRNK-16 leukemia in the rat: A role for NK cells

Roi Avraham*, Shelly Inbar, Ella Rosenne, Shamgar Ben-Eliyahu

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

It is unclear whether autologous immunity could be recruited to restrict the progression of leukemia. Patients harboring leukemia commonly display suppressed cell mediated immunity, which may contribute to their inability to control the disease. Immune response against leukemia is evident in allogeneic HLA-mismatched bone marrow transplantation, implicating the involvement of NK cells. This graft-versus-leukemia (GVL) activity suggests that, if not suppressed, an autologous NK cell response could potentially control acute leukemia that had down-regulated HLA expression. In the current study we assessed the role of non-suppressed autologous NK cells in controlling a syngeneic highly malignant leukemia, the CRNK-16 line, that constitute a major cause of natural death in aged F344 rats. A minuscule dose of 60 CRNK-16 leukemia cells per rat was sufficient to induce 50% mortality rates, and animals that survived this challenge did not show improved survival upon a second challenge. The CRNK-16 line was found to exhibit low levels of MHC-I, and selective in vivo depletion of NK cells nullified in vitro NK activity against the CRNK-16 line and reduced survival rates from this leukemia. In vivo activation of NK cells, employing low doses of poly I-C or IL-12, increased in vitro NK activity against the leukemia and dramatically improved survival rates when treatment was initiated before, but not after leukemia inoculation. These results indicate the ability of competent autologous NK cells to restrict highly malignant non-immunogenic leukemia. Thereby, this model presents an opportunity to study specific in vivo NK-leukemia interactions.

Original languageEnglish
Pages (from-to)1348-1357
Number of pages10
JournalCancer Immunology, Immunotherapy
Volume55
Issue number11
DOIs
StatePublished - Nov 2006

Keywords

  • Leukemia
  • Natural-killer cells
  • Rats
  • Tumor immunotherapy

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