Interleukin-10 knockout dendritic cells enhance suppression of tumor growth Free

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Cell-mediated immune responses supported by Th1-type cells are essential in the immune reaction against tumors, and they have the potential to prevent the tumor metastasis. Recent studies in animal models indicate that tumors by autocrine signaling are capable of immune suppression and escape by producing several mediators, such as IL10 which is an anti-inflammatory cytokine and negative regulator of Th1 cell-mediated immune response. In addition, dendritic antigen-presenting cells (APC) from the bone marrow and peripheral blood can present a variety of antigens, including tumor-associated antigens to the immune system. Based on these information we tested the hypothesis that IL-10 deficient dendritic cells (DC) pulsed ex-vivo with tumor associated antigens influence tumor progression. Tumor associated antigens (TAA) were collected by centrifugation from freeze-thawed confluent S1509s spindle tumor cells. Bone marrow derived DCs from wildtype (IL10 +/+) and IL10 knockout (IL10 -/-) mice were pulsed ex-vivo with TAA and used to immunize naïve animals. One week later the immunized animals and controls were challenged with live S1509a cells. Tumor growth was assessed every 48 h, and cytokine levels measured by ELISA. Higher levels of Th1 type cytokines and reduced tumor growth were seen in the animals immunized with IL-10KO DC pulsed with TAA. The fact that the animals treated with TAA pulsed DCs from IL-10 knockout mice had less incidents of tumor development might suggest that the control of tumor development in this study was facilitated by Th1 immune response. These primed Th1 cells are responsible for controlling tumor development when the animals were challenged with S1509a tumor cells. The adjuvant effects of the DCs, presentation of tumor antigens to Th1 cells, promotion of Th1 cell activation have important implications in the development of novel anti-tumor therapies and delivery of cancer prevention strategies.