title: Host-derived interleukin-1alpha is important in determining the immunogenicity of 3-methylcholantrene tumor cells.
abstract: Using IL-1/IL-1Ra knockout BALB/c mice, we showed that 3-methylcholatrene (3-MCA)-induced carcinogenesis is dependent on IL-1beta-induced inflammatory responses. Patterns of local inflammation and tumorigenicity were similar in wild-type (WT) and IL-1alpha(-/-) mice, while in IL-1beta(-/-) 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-1alpha(-/-) mice formed tumors only in immunocompromized mice. 3-MCA-induced fibrosarcoma cell lines from IL-1alpha(-/-) 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-1alpha(-/-) 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-1alpha(-/-) mice, in contrast to WT mice. Thus, we demonstrate in this study the significance of host-derived IL-1alpha 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-1alpha and IL-1beta in tumorigenesis; host-derived IL-1beta mainly controls inflammation, while concomitantly, IL-1alpha 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.
authors.affiliation: The Shraga Segal Department of Microbiology and Immunology and Faculty of Health Sciences and The Cancer Research Center, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
authors.forename: Moshe
authors.initials: M
authors.lastname: Elkabets
authors.forename: Yakov
authors.initials: Y
authors.lastname: Krelin
authors.forename: Shahar
authors.initials: S
authors.lastname: Dotan
authors.forename: Adelheid
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authors.lastname: Cerwenka
authors.forename: Angel
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authors.lastname: Porgador
authors.forename: Rachel G
authors.initials: RG
authors.lastname: Lichtenstein
authors.forename: Malka R
authors.initials: MR
authors.lastname: White
authors.forename: Margot
authors.initials: M
authors.lastname: Zoller
authors.forename: Yoichizo
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authors.lastname: Iwakura
authors.forename: Charles A
authors.initials: CA
authors.lastname: Dinarello
authors.forename: Elena
authors.initials: E
authors.lastname: Voronov
authors.forename: Ron N
authors.initials: RN
authors.lastname: Apte