Taking lessons from dendritic cells: multiple xenogeneic ligands for leukocyte integrins have the potential to stimulate anti-tumor immunity

Expression of large numbers of different costimulatory integrin ligands (CI Ls) attributes dendritic cells with an ability to induce primary anti-tumor immune responses. Here, we show that optimized gene transfer of the xenoge neic (human) CILs VCAM-1, MAdCAM-1 and ICAM-1 causes rapid and complete rej ection of established mouse EL-4 tumors, and generates prolonged systemic a nti-tumor immunity; whereas human E-cadherin weakly stows tumor growth. In each case the immune response was mediated by CD8(+) T cells and NK cells, accompanied by augmented tumor-specific cytolytic T cell (CTL) activity inv olving both the perforin and Fas-ligand pathways. Adoptive transfer of sple nocytes from cured mice rapidly cleared established tumors in recipients. T he mechanism for CIL-mediated immunity is unknown, but may involve CTL-faci litated tumor lysis, since CTLs were generally twice as efficient at killin g CIL-transfected tumor cells than parental tumor cells. Optimized CIL-base d gene therapy may provide an approach to complement or replace conventiona l DC adoptive cell therapy for suppressing tumor growth.