Adoptive immunotherapy of established tumors. Acquisition of radioresistance by tumor-specific T cells after passive transfer into tumor-bearing recipients.

Abstract

The present study was undertaken to determine the sensitivity to ionizing irradiation of T cells from mice immunized against the Meth-A fibrosarcoma and P815 mastocytoma after the transfer of these cells into tumor-bearing recipients. It was found that T cells from memory-immune donors were destroyed by exposing recipients to 500 rad of gamma irradiation up to 48 hr after transfer of the cells, but not thereafter. In contrast, activated immune cells were resistant to irradiation immediately after transfer. T cells were considered to be actively immune if they were harvested from donors in the process of rejecting their tumor, and were replicating, as evidenced by sensitivity to vinblastine. Memory-immune cells, on the other hand, were T cells that were harvested long after rejection of the immunizing tumor and were vinblastine-resistant. Additional results showed that CD8+ memory T cells were needed to cause regression of Meth-A tumor in recipients, whereas CD4+ memory T cells were needed for P815 tumor regression. These results support the idea that T cells that mediate tumor regression in this model of adoptive immunotherapy are radiosensitive while resting, and radioresistant after becoming activated. This knowledge needs to be taken into account when considering ionizing radiation as an immunomodulating agent for tumor immunotherapy.