Tumor's other immune targets: dendritic cells

The induction of apoptosis in T cells is one of several mechanisms by which tumors escape immune recognition. We have investigated whether tumors indu ce apoptosis in dendritic cells (DC) by co-culture of murine or human DC wi th different tumor cell lines for 4-48 h. Analysis of DC morphological feat ures, JAM assay, TUNEL, caspase-3-like and transglutaminase activity, Annex in V binding, and DNA fragmentation assays revealed a time- and dose-depend ent induction of apoptosis in DC by tumor-derived factors. This finding is both effector and target specific. The mechanism of tumor-induced DC apopto sis involved regulation of Bcl-2 and Bar expression. Double staining of bot h murine and human tumor tissues confirmed that tumor-associated DC undergo apoptotic death in vivo. DC isolated from tumor tissue showed significantl y higher levels of apoptosis as determined by TUNEL assay when compared wit h DC isolated from spleen. These findings demonstrate that tumors induce ap optosis in DC and suggest a new mechanism of tumor escape from immune recog nition. DC protection from apoptosis will lead to improvement of DC-based i mmunotherapies for cancer and other immune diseases.