Opposing effects of fibrosarcoma cell-derived IL-1 alpha and IL-1 beta on immune response induction

Int J Cancer. 2008 Jul 1;123(1):134-45. doi: 10.1002/ijc.23503.


There is evidence that cell-associated IL-1 alpha 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-1 alpha-, IL-1 beta- or IL-1a beta-knockout (IL-1 alpha(-/-), IL-1 beta(-/-), IL-1 alphabeta(-/-)) C57BL6 mice. The wt, IL-1 alpha(-/-), IL-1 beta(-/-) and IL-1 alphabeta(-/-) 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-1 beta(-/-) tumors rarely grow in the syngeneic host, which is the consequence of a strong T helper and CTL response induction by IL-1 alpha-competent, IL-1 beta(-/-) tumors. On the other hand, IL-1 beta-competent, IL-1 alpha(-/-) 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-1 alphabeta(-/-) tumors, the absence of IL-1 alpha becomes decisive, i.e. despite reduced suppressor cell recruitment, tumor growth was unimpaired due to inefficient immune response induction. Thus, sarcoma cell-derived IL-1 alpha and IL-1 beta do not act in concert. Induction of a strong immune response by IL-1 alpha demands therapeutic exploitation, which may become more efficient if systemic induction of immunosuppression by IL-1 beta can also be circumvented.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Fibrosarcoma / chemically induced
  • Fibrosarcoma / immunology*
  • Flow Cytometry
  • Immune Tolerance
  • Interleukin-1alpha / immunology*
  • Interleukin-1alpha / pharmacology
  • Interleukin-1beta / immunology*
  • Interleukin-1beta / pharmacology
  • Methylcholanthrene
  • Mice
  • Mice, Inbred C57BL
  • Mice, Nude
  • Specific Pathogen-Free Organisms
  • T-Lymphocytes, Cytotoxic
  • Tumor Cells, Cultured


  • Interleukin-1alpha
  • Interleukin-1beta
  • Methylcholanthrene