A novel vicious cycle cascade in tumor chemotherapy

Dendritic cells (DCs) play a critical role in both the cellular and humoral immune response to tumor cells. The participation of co-stimulator molecules on DCs is of vital importance for full activation of T cells. Conventional tumor chemotherapy cannot only induce apoptosis of malignant cells, but also do harm to benign DCs. Expression levels of co-stimulatory molecules (especially CD80 and CD86) are downregulated during anticancer drug treatment. These DCs are defective in their antigen-presenting function being tack of sufficient co-stimulatory molecules. Immune defective DCs provide negative immune signals to CD4+ and CD8+ T cells. Thereby these T cells are induced to become tolerant to the tumor cells, and function as T regulatory/suppressor cells to induce tolerogenic DCs by cell-cell contact. These DCs tolerized to tumor antigens may further render tolerogenicity to many more T cells via intercellular contact, and thus lead to a vicious cycle cascade. This model allowed us to envisage modified strategies of antitumor chemotherapy. We may use anticancer drugs with higher specificity to tumor cells, or in combination with immunopotentiator to disrupt the vicious cycle cascade, and expect better clinical result. (C) 2007 Elsevier Ltd. All rights reserved.