It is possible to cause the regression of a 4-day established tumor in a gamma-irradiated recipient by infusing the recipient with one organ equivalent of splenic T cells from a donor bearing a 9-day, progressive lethal tumor. This finding provides a powerful adoptive immunization assay to follow the generation of concomitant antitumor immunity to progressive tumor growth. Experiments with the SA1 sarcoma, Meth A fibrosarcoma, P815 mastocytoma, P388 lymphoma, and L5178Y lymphoma revealed that progressive tumor growth evoked the generation of tumor-sensitized T cells that, on passive transfer, could cause the regression of an established tumor in a gamma-irradiated (500 rad) recipient. These T cells were first detected on day 6 of tumor growth, reached peak numbers on days 9 to 10, and were then progressively lost as the tumor increased in size. Only splenic T cells harvested on days 9 to 10 had the capacity to cause complete and permanent regression of the recipient's tumor. The generation and loss of T cells capable of adoptively immunizing against an established tumor corresponded temporally to the acquisition and loss of concomitant immunity to growth of a tumor cell implant. It was next shown, with the Meth A fibrosarcoma and P815 mastocytoma, that the progressive loss after day 9 of T cells capable of adoptively immunizing against an established tumor was associated with the progressive acquisition of splenic suppressor T cells capable of inhibiting the capacity of tumor-sensitized T cells from preimmunized donors to cause the regression of an established tumor in T cell-deficient (TXB) recipients. These findings are consistent with the hypothesis that there is progressive growth of a concomitant immune response that is actively down-regulated by suppressor T cells before it reaches sufficient magnitude to destroy the tumor. The adoptive immunization assay showed that the T cells that mediate concomitant immunity are Ly1?-?2?+? T cells. In contrast, the cells which suppress the immunity are Ly1?+?2?-?i T cells. Additional experiments have revealed that suppressor T cells function in the adoptive immunization assay by inhibiting the ability of passively transferred helper or memory T cells to give rise to an adoptive cytolytic T-cell response in the tumor-bearing recipient. A knowledge of the kinetics of the generation and T cell-mediated suppression of the concomitant anti-tumor immune response is crucial for the design of successful immunotherapeutic modalities. The experimental results indicate that any attempt to treat a tumor by active or passive immunotherapy represents an attempt to superimpose an immune response on an ongoing concomitant immune response that may be undergoing negative regulation. (TA)
Showing the most recent 10 out of 31 publications
