ABSTRACT
BACKGROUND: The progression of prostate cancer is accompanied by a marked suppression of the immune system, including the apoptotic death of dendritic cells (DC) responsible for the induction of antitumor immunity. In this study, we evaluated whether prostate cancer might inhibit DC generation and maturation in vitro. METHODS: DC were generated from peripheral blood monocytes in the presence of the human prostate cell line LNCaP or nonmalignant cells, and characterized by light microscopy, FACScan analysis, and ability to stimulate T-cell proliferation. RESULTS: Prostate cancer significantly inhibited the conversion of monocytes into DC, which was assessed by the expression of DC markers CD1a and CD83. These cells were weak stimulators of T-cell proliferation, suggesting that DC generated in the prostate cancer microenvironment are functionally inhibited. CONCLUSIONS: Prostate cancer not only kills mature DC, but also inhibits their generation and maturation, resulting in decreased production of antigen-presenting cells and inhibition of their functional activity.
Subject(s)
Dendritic Cells/immunology , Prostatic Neoplasms/immunology , Antigens, CD , Antigens, CD1/analysis , Dendritic Cells/pathology , Flow Cytometry , Histocytochemistry , Humans , Immunoglobulins , Lymphocyte Culture Test, Mixed , Male , Membrane Glycoproteins , Monocytes/immunology , Monocytes/pathology , Prostatic Neoplasms/pathology , Scintillation Counting , Tritium , Tumor Cells, Cultured , CD83 AntigenABSTRACT
Systemic immunotherapy, notably with interleukin-2 (IL-2) and interferon-alpha (IFNalpha), has yielded a response rate of 10 % to 30 % in metastatic renal cell carcinoma. However, systemic immunotherapy is limited by severe side effects, and long-lasting response is rare. Tumor palliation and quality-of-life are important end points for evaluating the clinical benefits of immunotherapy. Experimental and clinical treatment models have proved that local IL-2 application is less toxic than systemic treatment and is therapeutically effective. Here we report long-term experience with inhalation IL-2 therapy in 188 patients who had progressive pulmonary metastatic renal cell carcinoma. High-dose inhalation of IL-2 was used with low-dose systemic IL-2 or IFNalpha. Maximal toxicity over the total treatment time was mild, and the low incidence of WHO grade 3 toxicity (24 %) allowed social activities and performance of social roles. Comedication for systemic side effects was required only in half of the patients. Inhaled IL-2 prevented progress of pulmonary metastases in 68 % of patients for a median period of 9.8 months. Median survival was 12.4 months compared with the expected 5.3 months and quality-of-life did not differ substantially from pretreatment status. Local treatment can be applied alone or in combination with systemic therapy and can increase therapeutic efficacy.
