Immune phenomena involved in the in vivo regression of fibrosarcoma cells expressing cell-associated IL-1α

Tatyana Dvorkin, Xiaoping Song, Shmuel Argov, Rosalyn M. White, Margot Zoller, Shraga Segal, Charles A. Dinarello, Elena Voronov, Ron N. Apte

Research output: Contribution to journalArticlepeer-review

41 Scopus citations

Abstract

Constitutive expression of cell-associated, but not secreted, interleukin-1α (IL-1α) by oncogene-transformed fibrosarcoma cells induced regressing tumors in mice, a phenomenon that was abrogated by the IL-1 inhibitor, the IL-1 receptor antagonist (IL-1Ra). On the contrary, non-IL-1α-expressing tumor cells induce progressive tumors in mice. In vivo and ex vivo experiments have shown that regression of IL-1α-positive fibrosarcoma cells depends on CD8 + T cells, which can also be activated in CD4 + T cell-depleted mice, with some contribution of natural killer cells. In spleens of mice bearing the non-IL-1α-expressing fibrosarcoma cells, some early and transient manifestations of antitumorspecific immunity, such as activation of specific proliferating T cells, are evident; however, no development of cytolytic T lymphocytes or other antitumor protective cells could be detected. In spleens of mice bearing the non-IL-1α- expressing fibrosarcoma cells, the development of early tumor-mediated suppression was observed, and in spleens of mice injected with IL-1α-positive fibrosarcoma cells, protective immunity developed in parallel to tumor regression. Treatment of mice bearing violent fibrosarcoma tumors with syngeneic-inactivated, IL-1α-positive fibrosarcoma cells, at a critical interval after injection of the malignant cells (Days 5-12), induced tumor regression, possibly by potentiating and amplifying transient antitumor cell immune responses or by ablation of tumor-mediated suppression. Membrane-associated IL-1α may thus serve as an adhesion molecule, which allows efficient cell-to-cell interactions between the malignant and immune effector cells that bear IL-1Rs and function as a focused cytokine with adjuvant activities at nontoxic, low levels of expression. Our results also point to the potential of using antitumor immunotherapeutic approaches using cell-associated IL-1α.

Original languageEnglish
Pages (from-to)96-106
Number of pages11
JournalJournal of Leukocyte Biology
Volume80
Issue number1
DOIs
StatePublished - 1 Jul 2006

Keywords

  • Interleukin-1
  • Protective immunity

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Cell Biology

Fingerprint

Dive into the research topics of 'Immune phenomena involved in the in vivo regression of fibrosarcoma cells expressing cell-associated IL-1α'. Together they form a unique fingerprint.

Cite this