Tumor cell-induced deactivation of human monocytes
| Autor: | Irena Ruggiero, Marek Zembala, Monika Baj-Krzyworzeka, Maciej Siedlar, Rafał Szatanek, M. Woloszyn, Jerzy Więckiewicz, Bozenna Mytar |
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| Rok vydání: | 2003 |
| Předmět: |
Lipopolysaccharides
Lipopolysaccharide medicine.medical_treatment Immunology Tumor Infiltrating Macrophages Down-Regulation Hyaluronoglucosaminidase Neuraminidase Biology Monocytes chemistry.chemical_compound Adjuvants Immunologic Neoplasms Tumor Cells Cultured medicine Humans Immunology and Allergy Cytotoxic T cell Hyaluronic Acid Interleukin-12 Subunit p40 Reverse Transcriptase Polymerase Chain Reaction Tumor Necrosis Factor-alpha Monocyte Receptors Interleukin-1 Cell Biology Interleukin-12 Coculture Techniques Interleukin-10 Protein Subunits Hyaluronan Receptors Interleukin-1 Receptor-Associated Kinases medicine.anatomical_structure Cytokine chemistry Cancer cell Cancer research Cytokines Interleukin 19 Tumor necrosis factor alpha Protein Kinases |
| Zdroj: | Journal of Leukocyte Biology. 74:1094-1101 |
| ISSN: | 1938-3673 0741-5400 |
| DOI: | 10.1189/jlb.0403140 |
| Popis: | Although blood monocytes exhibit significant cytotoxic activity against tumor cells, the function of tumor infiltrating macrophages (TIM) is depressed in cancer patients. This study addresses the question of how the antitumor response of human monocytes, assessed by production of cytokines (tumor necrosis factor α, TNF; IL-10; IL-12p40) and cytotoxicity, is altered by exposure to cancer cells. Tumor cell−pre-exposed monocytes restimulated with tumor cells showed significantly decreased production of TNF, IL-12, increased IL-10 (mRNA and release) and inhibition of IL-1 receptor-associated kinase-1 (IRAK-1) expression. This down-regulation of cytokine production was selective, as the response of pre-exposed monocytes to lipopolysaccharide (LPS) was unaffected. Treatment of tumor cell−pre-exposed monocytes with hyaluronidase (HAase) improved their depressed production of TNF, while HAase-treated cancer cells did not cause monocyte dysfunction. The response of hyaluronan (HA)−pre-exposed monocytes to stimulation with tumor cells was also inhibited. Cytotoxic activity of monocytes pretreated with cancer cells was also decreased. This study shows that tumor cells selectively deactivate monocytes and suggests that tumor cell-derived HA by blocking CD44 on monocytes inhibits their antitumor response. These observations may provide some explanation for the depressed function of TIM in human malignancy. |
| Databáze: | OpenAIRE |
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