The induction of in vivo proliferation of long-lived CD44(hi) CD8+ T cells after the injection of tumor cells expressing IFN-α1 into syngeneic mice

Filippo Belardelli, Maria Ferrantini, Stefano M. Santini, Sara Baccarini, Enrico Proietti, Mario P. Colombo, Jonathan Sprent, David F. Tough

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Abstract

The tumorigenicity of transplantable tumor cells in mice is reduced by transduction with cytokine genes, including IFN-α and interleukin (IL) 12. Although T cells are considered important in tumor rejection, the mechanism by which genetically modified tumor cells stimulate the immune system has not been examined. In this study, the in vivo proliferation of T-cell subsets in mice transplanted with cytokine-producing syngeneic tumor cells was assessed by administering the DNA precursor bromodeoxyuridine. The injection of viable cells producing IFN-α or IL-12 caused a marked proliferation of CD8+ T lymphocytes in both the spleen and lymph nodes. Proliferation was most prominent among memory-phenotype CD44(hi) CD8+ T cells. In contrast, proliferation of CD8+ T cells did not occur in mice injected with control cells or with cells expressing IL-4, granulocyte colony-stimulating factor, or IFN-γ Pulse-chase studies in mice injected with IFN-α-producing cells showed that a proportion of proliferating CD8+ T cells survived for at least 70 days, suggesting that long-lived memory cells are induced using such an approach. In summary, these results, together with previous studies on the host immune reactivity triggered by the injection of tumor cells expressing IFN-α, represent a strong rationale for considering IFN-α as a powerful T- cell adjuvant for the generation of more effective cancer vaccines.

Original languageEnglish
Pages (from-to)5795-5802
Number of pages8
JournalCancer Research
Volume58
Issue number24
Publication statusPublished - Dec 15 1998

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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    Belardelli, F., Ferrantini, M., Santini, S. M., Baccarini, S., Proietti, E., Colombo, M. P., Sprent, J., & Tough, D. F. (1998). The induction of in vivo proliferation of long-lived CD44(hi) CD8+ T cells after the injection of tumor cells expressing IFN-α1 into syngeneic mice. Cancer Research, 58(24), 5795-5802.