GAMMA-IRRADIATION SUPPRESSES T-CELL MEDIATED PROTECTIVE IMMUNITY AGAINST A METASTATIC TUMOR IN THE AFFERENT PHASE OF THE IMMUNE-RESPONSE BUT ENHANCES IT IN THE EFFERENT PHASE WHEN GIVEN BEFORE IMMUNE CELL TRANSFER

Using a metastasizing animal tumor as a model we describe experimental conditions for obtaining either synergistic or antagonistic effects between host irradiation and T cell mediated antitumor immunity. The results were obtained in the well defined murine lymphoma ESb which is a spontaneous highly metastatic tumor variant expressing a tumor associated antigen that can induce protective immunity and tumor specific cytotoxic T lymphocyte (CTL) activity. Sublethal irradiation of mice during the afferent (induction) phase but not during the efferent (effector) phase of the antitumor immune response had a strong suppressive effect on protective immunity. The radiation mediated defect could be reconstituted by transfer of immune spleen cells. The immune system of syngeneic (DBA/2) and allogeneic (B10.D2) mice changed within 24 h after first contact with the ESb tumor cells from radio-sensitivity to radio-resistance possibly reflecting an active cellular response associated with the change from virgin to an antigen sensitized (primed) state of T lymphocyte differentiation. T cell depletion experiments revealed that the afferent phase was dependent on both CD4 and CD8 host T lymphocytes while the efferent phase was mainly CD8 T cell dependent. A synergistic effect between gamma-irradiation and antitumor immunity was observed in adoptive immunotherapy experiments. When tumor-bearing hosts were irradiated before intravenous transfer of either syngeneic or allogeneic antitumor immune T cells the expression of anti-metastatic protective immunity was greatly enhanced in comparison to identically treated non-irradiated hosts.