Expression and cytokine mediated modulation of adhesion/costimulation molecules ICAM-1(CD54) and LFA-3(CD58) in human ovarian cancer

Previous studies have shown that paracrine delivery of helper cytokines by transduced tumor cells can bypass the lack of the B7 costimulation pathway, which when engaged induces secretion of a number of cytokines, most notably IL-2 and which results in clonal T-cell proliferation and effector function. However, other costimulation signals such as those mediated by ICAM-1 and LFA-3 molecules remain crucial to increase antigen independent conjugate formation and therefore synergize with TcR activation pathways. In this study we have analyzed tumor cells from eight freshly isolated and histologically similar human ovarian tumors for their surface antigen expression of the adhesion/costimulation molecules ICAM-1 and LFA-3 before and after exposure to the cytokines TNF-α plus IFN-γ. All eight fresh tumors expressed variable levels of ICAM-1 antigens and these levels were markedly upregulated after exposure to TNF-α plus IFN-γ. Similarly, LFA-3 antigens were shown to be expressed in all fresh tumor evaluated. However, in contrast to the ICAM-1/LFA-1 pathway of costimulatory molecules, LFA-3/CD2 pathway was shown to be resistant to modulation with these cytokines. Such findings suggest that fresh ovarian tumor cells pretreated with TNF-α plus IFN-γ could significantly increase their adhesion/costimulation activity for T cell recognition when admixed with genetically manipulated tumor cells to be used as tumor vaccines.