title: Cytokine-induced tumor immunogenicity: endogenous interleukin-1 alpha expressed by fibrosarcoma cells confers reduced tumorigenicity.
abstract: A direct correlation between the constitutive expression of IL-1 alpha and reduced tumorigenicity of fibrosarcomas was observed. This was established in fibrosarcoma cell lines which produce IL-1 alpha 'spontaneously', possibly as an aberration of oncogene-mediated transformation or upon IL-1 alpha gene transfer. In fibroblasts intracellular or membrane-associated IL-1 alpha is expressed, whereas the secreted form of the cytokine (IL-1 beta) is absent. Studies on the mechanisms of tumor regression of the IL-1 alpha-positive fibroblastoid cell lines indicated that IL-1 alpha potentiates the development of tumor cell-specific CTLs, which are of importance for tumor eradication. Thus, IL-1 alpha induces enhanced helper T cell activity which provides auxiliary signals for the growth/development of CTLs. Non-adaptive effector cells, activated locally by IL-1 alpha-expressing fibrosarcoma cells, also contribute to the eradication of IL-1 alpha-expressing fibrosarcomas. Local IL-1 alpha expression potentiated antigen presentation, by the malignant fibroblasts as well as by tissue-resident antigen-presenting cells, thus further potentiating anti-tumor immune responses. Mice, in which IL-1 alpha-producing tumors were regressed, developed an immune memory and rejected a challenge with an IL-1 non-producing violent tumor cell line. Endogenous IL-1 alpha activates a cytokine cascade (i.e., IL-6, CSF), produced by the malignant cells and possibly also by stromal cells. However, IL-1 alpha expression is essential for fibrosarcoma eradication, while other cytokines possibly amplify and sustain its action.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Microbiology and Immunology, Faculty of Health Sciences, Ben-Gurion University, Beer-Sheva, Israel.
authors.forename: R N
authors.initials: RN
authors.lastname: Apte
authors.forename: A
authors.initials: A
authors.lastname: Douvdevani
authors.forename: M
authors.initials: M
authors.lastname: Zoller
authors.forename: R M
authors.initials: RM
authors.lastname: White
authors.forename: T
authors.initials: T
authors.lastname: Dvorkin
authors.forename: N
authors.initials: N
authors.lastname: Shimoni
authors.forename: E
authors.initials: E
authors.lastname: Fima
authors.forename: M
authors.initials: M
authors.lastname: Hacham
authors.forename: M
authors.initials: M
authors.lastname: Huleihel
authors.forename: D
authors.initials: D
authors.lastname: Benharroch
mesh_terms: D016475:3T3 Cells; D000818:Animals; D002471:Cell Transformation, Neoplastic; D005354:Fibrosarcoma / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D007167:Immunotherapy; D007375:Interleukin-1 / Q000096:biosynthesis*; D051379:Mice; D008819:Mice, Nude; D012074:Remission Induction; D014162:Transfection
chemical_list: D007375:Interleukin-1