Host-derived interleukin-1α is important in determining the immunogenicity of 3-methylcholantrene tumor cells

Moshe Elkabets, Yakov Krelin, Shahar Dotan, Adelheid Cerwenka, Angel Porgador, Rachel G. Lichtenstein, Malka R. White, Margot Zoller, Yoichizo Iwakura, Charles A. Dinarello, Elena Voronov, Ron N. Apte

Research output: Contribution to journalArticlepeer-review

32 Scopus citations

Abstract

Using IL-1/IL-1Ra knockout BALB/c mice, we showed that 3-methylcholatrene (3-MCA)-induced carcinogenesis is dependent on IL-1β-induced inflammatory responses. Patterns of local inflammation and tumorigenicity were similar in wild-type (WT) and IL-1α-/- mice, while in IL-1β -/- mice, tumorigenicity was attenuated and in IL-1Ra-/- mice accentuated. 3-MCA-induced fibrosarcoma cell lines from WT mice developed into progressive tumors in WT mice, while surprisingly, lines from IL-1α-/- mice formed tumors only in immunocompromized mice. 3-MCA-induced fibrosarcoma cell lines from IL-1α-/- mice, compared with lines from WT mice, manifested higher expression levels of "global" surface molecules related to Ag presentation and interactions with immune surveillance cells (MHC class I, B7.1, B7.2, L-selectin, and NKG2D ligands) and were eradicated mainly by CD4+-and CD8 +-dependent T cell responses. Concomitantly, at the injection site of 3-MCA-induced fibrosarcoma cells derived from IL-1α-/- mice, a leukocyte infiltrate, subsequently replaced by a scar-like tissue, was observed. Immune aberrations in NK cell maturation, antitumor specific immunity and killing capacity of effector cells were observed in IL-1α -/- mice, in contrast to WT mice. Thus, we demonstrate in this study the significance of host-derived IL-1α in cancer immunoediting, by affecting innate and specific immunosurveillance mechanisms. Overall, the results presented in this study, together with our previous studies, attest to differential involvement of IL-1α and IL-1β in tumorigenesis; host-derived IL-1β mainly controls inflammation, while concomitantly, IL-1α controls immunosurveillance of the arising malignant cells. Elucidation of the involvement of the IL-1 molecules in the malignant process will hopefully lead to the development of novel approaches for chemoprevention and immunotherapy.

Original languageEnglish
Pages (from-to)4874-4881
Number of pages8
JournalJournal of Immunology
Volume182
Issue number8
DOIs
StatePublished - 15 Apr 2009

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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