Selective Radiation Resistance of Immunologically Induced T Cells as the Basis for Irradiation-Induced T-Cell-Mediated Regression of Immunogenic Tumor

Sublethal, whole-body gamma-irradiation of immunocompetent, but not T cell deficient, mice bearing an established immunogenic tumor results in T-cell-mediated complete tumor regression and in long-term host survival. This striking T-cell-dependent immunotherapeutic action of irradiation was paradoxically associated with the destruction of over 90% of host T cells and with a state of severe immunodepression as evidenced by the inability of irradiated mice to reject a tumor allograft. Furthermore, whereas exposure to 500 rads caused regression of a syngeneic tumor implanted 6 days before irradiation, it caused enhanced growth of a different syngeneic tumor growing on the same animal and implanted 1 day before. This ability of irradiation to cause regression of a 6 day tumor, but accelerated growth of a 1 day tumor, was also seen when the tumors were implanted in the reverse order. This means that, between days 1 and 6 of a tumor growth, tumor-specific T cells are converted from a radiosensitive to a highly radioresistant state, almost certainly because of having been activated and inducted into the antitumor immune response. This explanation for the selective radioresistance of effector T cells is based on publications showing that activated, in contrast to resting, T cells are highly radioresistant. Thus irradiation-induced, T-cell-mediated tumor regression depends not only on the destruction of radiosensitive suppressor T cells but also on the selective sparing of radioresistant activated effector T cells that are needed to destroy the tumor in the absence of suppression.