Reduced T-Cell and Dendritic Cell Function Is Related to Cyclooxygenase-2 Overexpression and Prostaglandin E2 Secretion in Patients With Breast Cancer
| Autor: | Jose L. Hernandez, Barbara A. Pockaj, Richard Gray, Gargi D. Basu, Latha B. Pathangey, Sandra J. Gendler, Pinku Mukherjee |
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| Rok vydání: | 2004 |
| Předmět: |
Adult
T-Lymphocytes T cell medicine.medical_treatment Breast Neoplasms Disease Dinoprostone Breast cancer Immune system Surgical oncology Tumor Cells Cultured medicine Humans skin and connective tissue diseases Aged Aged 80 and over Immunosuppression Therapy business.industry Gene Expression Profiling Membrane Proteins Immunosuppression Dendritic Cells Dendritic cell Middle Aged biochemical phenomena metabolism and nutrition Prognosis medicine.disease Gene Expression Regulation Neoplastic Isoenzymes Phenotype medicine.anatomical_structure Oncology Cyclooxygenase 2 Prostaglandin-Endoperoxide Synthases Case-Control Studies Immunology Disease Progression Cancer research Female Surgery business Cell Division Prostaglandin E |
| Zdroj: | Annals of Surgical Oncology. 11:328-339 |
| ISSN: | 1534-4681 1068-9265 |
| Popis: | In several neoplastic diseases, including breast cancer, immunosuppression correlates with disease stage, progression, and outcome. Thus, thorough analysis of immune parameters in breast cancer patients may be beneficial in designing effective anticancer immune-based therapies.We investigated dendritic cell and T-cell function in breast cancer patients at various stages of the disease and in age-matched controls. We also evaluated cyclooxygenase-2 (COX-2) expression and prostaglandin E2 (PGE2) levels within the tumor milieu and in the circulation.T cells from cancer patients showed decreased proliferation in response to CD3 antibody stimulation. Analysis of T-cell helper type 1 and 2 cytokines revealed reduced levels of interferon-gamma, tumor necrosis factor-alpha, interleukin (IL)-12, and IL-2 and increased levels of IL-10 and IL-4. Dendritic cells from these patients showed significantly reduced expression of co-stimulatory molecules (B7 and CD40) and demonstrated reduced phagocytic ability, reduced antigen presentation to T cells, and reduced ability to mature in response to lipopolysaccharide. Data revealed increased synthesis of PGE2, an immune suppressor, along with increased expression of COX-2, a key regulator of PGE2 synthesis.COX-2-induced PGE2 may contribute to immunosuppression and may directly block antitumor immunity while promoting tumor growth, providing us with the rationale for using COX-2 inhibition combined with immunotherapy. |
| Databáze: | OpenAIRE |
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