Radiosensitive barrier to T-cell-mediated adoptive immunotherapy of established tumors

Abstract

This study shows that it is not possible to cause regression of the immunogenic SA-1 sarcoma by adoptive immunotherapy with tumor-sensitized T-cells, unless the tumor-bearing recipient is exposed to a sublethal dose of gamma-irradiation to remove a barrier that prevents adoptive immunity from being expressed. This barrier to adoptive immunotherapy was found to be regenerated between 2 and 4 weeks following irradiation, and its regeneration was associated with general repopulation of host T-cells. However, it was not regenerated in the absence of the thymus, thus showing that it is T-cell dependent. Evidence that it is caused by the presence of CD4+ suppressor T-cells was shown by the finding that it can be removed by depleting mice of CD4+ T-cells with anti-L3T4 monoclonal antibodies, but not by depleting them of CD8+ T-cells with anti-Lyt-2 monoclonal antibodies. Again, the barrier could be restored to irradiated recipients by infusing them with CD4+ T-cells, but not with CD8+ T-cells, from tumor-bearing donors. The barrier to adoptive immunotherapy was found to be tumor induced and to be paradoxically generated in concert with host concomitant immunity.