Opposing effects of fibrosarcoma cell-derived IL-1α and IL-1β on immune response induction

Rachid Marhaba, Irina Nazarenko, Daniela Knöfler, Eli Reich, Elena Voronov, Mario Vitacolonna, Dagmar Hildebrand, Elena Elter, Ron N. Apte, Margot Zöller

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

There is evidence that cell-associated IL-1α supports immune response induction. Here we explored the impact of malignant cell-derived IL-1 on immunogenicity, immune response induction and tumor-induced immunosuppression using 3-methylcholanthrene-induced fibrosarcoma lines derived from wild-type (wt), IL-1α-, IL-1β- or IL-1aβ-knockout (IL-1α -/-, IL-1β-/-, IL-1αβ-/-) C57BL6 mice. The wt, IL-1α-/-, IL-1β-/- and IL-1αβ-/- fibrosarcoma lines express MHC class I molecules at a high level. The lines do not differ in their susceptibility toward NK cells, macrophages, and allogeneic CTL, or in their capacity as stimulators of an allogeneic response. However, IL-1β-/- tumors rarely grow in the syngeneic host, which is the consequence of a strong T helper and CTL response induction by IL-1α-competent, IL-1β-/- tumors. On the other hand, IL-1β-competent, IL-1α-/- tumors strongly assist CD11b+Gr-1+ myeloid-derived suppressor cell and regulatory T cell expansion, which both suppress with high efficacy activated T helper cell proliferation and CTL lysis. In IL-1αβ-/- tumors, the absence of IL-1α becomes decisive, i.e. despite reduced suppressor cell recruitment, tumor growth was unimpaired due to inefficient immune response induction. Thus, sarcoma cell-derived IL-1α and IL-1β do not act in concert. Induction of a strong immune response by IL-1α demands therapeutic exploitation, which may become more efficient if systemic induction of immunosuppression by IL-1β can also be circumvented.

Original languageEnglish
Pages (from-to)134-145
Number of pages12
JournalInternational Journal of Cancer
Volume123
Issue number1
DOIs
StatePublished - 1 Jul 2008

Keywords

  • Fibrosarcoma
  • Mouse
  • Myeloid-derived suppressor cells
  • Regulatory T-cells
  • T-cell response

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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