Immune phenomena involved in the in vivo regression of fibrosarcoma cells expressing cell-associated IL-1alpha
| Autor: | Margot Zöller, Ron N. Apte, Xiaoping Song, Tatyana Dvorkin, Elena Voronov, Shmuel Argov, Shraga Segal, Rosalyn M. White, Charles A. Dinarello |
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| Rok vydání: | 2006 |
| Předmět: |
ZAP70
Fibrosarcoma Immunology Mice Inbred Strains Cell Biology Biology CD8-Positive T-Lymphocytes medicine.disease Natural killer T cell Interleukin 21 Mice Immune system Neoplasm Regression Spontaneous Cell Line Tumor Interleukin-1alpha medicine Cancer research Interleukin 12 Immunology and Allergy Cytotoxic T cell Animals IL-2 receptor |
| Zdroj: | Journal of leukocyte biology. 80(1) |
| ISSN: | 0741-5400 |
| Popis: | 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 antitumor-specific 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. |
| Databáze: | OpenAIRE |
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