CD83, a characteristic marker of activated dendritic cells, is also expressed by tumor cell lines from various origins and by primary lung cancers. Here, we show that CD83+ tumor cells (from a primary lung cancer and from an established breast cancer cell line) release in their culture supernatants a soluble factor that is able to block, in a dose-dependent manner, CD4+ and CD8+ T cell proliferative responses to allogeneic dendritic cells. This factor was removed from the medium by incubation in anti-CD83 covered plates, indicating that it could be one of the known soluble forms of the CD83 molecule, released in the medium by the cultured tumor cells. This phenomenon, happening in vivo, in the tumor microenvironment, could affect profoundly anti-tumor immune responses and should, therefore, be considered in immunotherapeutic approaches to cancer.