Host-Derived Interleukin-1α Is Important in Determining the Immunogenicity of 3-Methylcholantrene Tumor Cells

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