Author:

Keywords:

tumor immunology, renal cell carcinoma, hemato-oncology, cd80/cd86-cd28 interaction, cd40-cd154 interaction, t-cell activation, antigen-presenting cells, reed-sternberg cells, dendritic cells, cyclosporine-a, tumor-cells, b-cells, monoclonal-antibody, cytokine production, antitumor immunity, Science & Technology, Life Sciences & Biomedicine, Oncology, Pediatrics, CD80/CD86-CD28 interaction, CD40-CD154 interaction, T-CELL ACTIVATION, ANTIGEN-PRESENTING CELLS, REED-STERNBERG CELLS, DENDRITIC CELLS, CYCLOSPORINE-A, TUMOR-CELLS, B-CELLS, MONOCLONAL-ANTIBODY, CYTOKINE PRODUCTION, ANTITUMOR IMMUNITY, Humans, Immune System, Lymphocyte Activation, Neoplasms, T-Lymphocytes, 1103 Clinical Sciences, 1112 Oncology and Carcinogenesis, 1114 Paediatrics and Reproductive Medicine, Oncology & Carcinogenesis, 3211 Oncology and carcinogenesis, 3213 Paediatrics

Abstract:

Insights into the mechanisms of T cell activation have improved markedly over the last decades. Besides the interaction between the antigen and the T cell receptor, the specific role of costimulatory molecule interactions such as the CD80/CD86-CD28 and the CD40-CD154 interaction forms the basis of the multiple step T cell activation model. The costimulatory capacity of CD28 for the production of Th0, Th1 and Th2 cytokines by T cells and for the generation of cytotoxic T cell activity has clearly been demonstrated. Although activation of the immune status could be demonstrated in renal cell carcinoma patients and in patients with hematologic malignancies, ex vivo tumor-specific killing activity by T cells was not found. Moreover, even after manipulating B-CLL tumor cells through CD40 triggering, antitumoral T cell cytotoxicity could not be elicited in vitro. Nowadays, based on new insights into the differentiation and activation of blood- or bone marrow- derived dendritic cells, ex vivo loading of DC with tumor antigens, and in vivo stimulation of putative tumor-specific circulating T cells through vaccination with tumor-loaded DC, represents a new approach towards an effective antitumoral immune strategy.