T cell-mediated immunosuppression as an obstacle to adoptive immunotherapy of the P815 mastocytoma and its metastases.

Abstract

Progressive growth of the [mouse] P815 mastocytoma cells in semisyngenic mice evokes the generation of a T cell-mediated mechanism of immunosuppression that inhibits the capacity of passively transferred, tumor-sensitized T cells from regressing this tumor in recipient mice. This conclusion is based on the following 2 findings: it is possible to demonstrate adoptive T cell-mediated regression of established tumors, but only if the tumors are growing in T cell-deficient recipients; adoptive T cell-mediated regression of tumors in these recipients can be inhibited by the infusion of splenic T cells from T cell-intact, tumor-bearing donors. The results of additional experiments designed to measure the effect of decreasing the number of suppressor cells and the time that they are infused, relative to immune cells, indicate that the function of suppressor cells in this model is to inhibit the replication of passively transferred immune T cells. The results obtained with the P81S mastocytoma are similar to those obtained previously with a chemically induced fibrosarcoma. They show, in addition, that passively transferred immune cells are capable of destroying already seeded metastases in T cell-deficient recipients.