CD11b+/Gr-1+ immature myeloid cells mediate suppression of T cells in mice bearing tumors of IL-1beta-secreting cells
| Autor: | Elena Voronov, Ron N. Apte, Shraga Segal, Xiaoping Song, Yakov Krelin, Tatyana Dvorkin, Olle Bjorkdahl, Charles A. Dinarello |
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| Rok vydání: | 2005 |
| Předmět: |
medicine.medical_specialty
Chemokine Angiogenesis T cell Sialoglycoproteins T-Lymphocytes Immunology Spleen Biology Proinflammatory cytokine Mice Immune system Internal medicine medicine Immunology and Allergy Animals Myeloid Cells Neoplasm Invasiveness Leukocytosis Fibrosarcoma CD11b Antigen Neovascularization Pathologic Receptors Interleukin-1 Neoplasms Experimental medicine.disease Coculture Techniques Tumor Burden Interleukin 1 Receptor Antagonist Protein medicine.anatomical_structure Endocrinology Cancer research biology.protein Receptors Chemokine medicine.symptom Interleukin-1 |
| Zdroj: | Journal of immunology (Baltimore, Md. : 1950). 175(12) |
| ISSN: | 0022-1767 |
| Popis: | Tumor cells secreting IL-1β are invasive and metastatic, more than the parental line or control mock-transfected cells, and concomitantly induce in mice general immune suppression of T cell responses. Suppression strongly correlates with accumulation in the peripheral blood and spleen of CD11b+/Gr-1+ immature myeloid cells and hematological alterations, such as splenomegaly, leukocytosis, and anemia. Resection of large tumors of IL-1β-secreting cells restored immune reactivity and hematological alterations within 7–10 days. Treatment of tumor-bearing mice with the physiological inhibitor of IL-1, the IL-1R antagonist, reduced tumor growth and attenuated the hematological alterations. Depletion of CD11b+/Gr-1+ immature myeloid cells from splenocytes of tumor-bearing mice abrogated suppression. Despite tumor-mediated suppression, resection of large tumors of IL-1β-secreting cells, followed by a challenge with the wild-type parental cells, induced resistance in mice; protection was not observed in mice bearing tumors of mock-transfected fibrosarcoma cells. Altogether, we show in this study that tumor-derived IL-1β, in addition to its proinflammatory effects on tumor invasiveness, induces in the host hematological alterations and tumor-mediated suppression. Furthermore, the antitumor effectiveness of the IL-1R antagonist was also shown to encompass restoration of hematological alterations, in addition to its favorable effects on tumor invasiveness and angiogenesis that have previously been described by us. |
| Databáze: | OpenAIRE |
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