MODIFICATION OF TUMOR MICROENVIRONMENT BY CYTOKINE GENE-TRANSFER

The tumor microenvironment is determined by the interactions between h ost and tumor cells, a process in which cytokines play a major role. W e have used retroviral vectors to insert and express cytokine genes in tumor cells so as to induce predictable changes in the host cells tha t infiltrate tumors. This frequently caused changes in tumor cell phen otype through autocrine/intracrine pathways. We reasoned that cytokine -induced alterations in tumor cell phenotype and/or in infiltrating ho st cells might alter the in vitro and in vivo cellular response to irr adiation. In the present paper we document some of the effects of expr ession of interleukin-6 (IL-6) and IL-7 genes in tumor cells in this r egard. The studies support the hypothesis that cytokines may play a ro le in determining both intrinsic tumor radioresponsiveness and the tum or microenvironment and in these ways may influence in vivo tumor irra diation responses. Possible cytokine gene-mediated approaches to radio therapy cancer are discussed.