The CD4 cell dependency of SJL/J B-cell lymphomas as a target for cyclophosphamide therapy.

SJL/J B-cell lymphomas induce proliferation of syngeneic CD4 cells, on which the tumors are dependent for growth. We sought to determine whether cyclophosphamide (CY) treatment of tumor-bearing mice would be successful through effects on tumor cells, CD4 cells, or both. The markedly increased survival of treated mice derived predominantly from reduced proliferation of CD4 cells in response to tumor. Reduced proliferation of CD4 cells created a microenvironment that was not conducive to tumor growth, as evidenced by the failure of a subsequent tumor cell challenge to treated mice to significantly increase the rate of the mice. We concluded that CY affected the tumor-stimulated environment of SJL/J mice by killing CD4 cells that had been activated by a pre-existing tumor stimulus and by promoting the appearance of a population of CD8 cells that suppressed the ability of residual or recovering CD4 cells to proliferate in response to tumor. The CD8 population from treated mice was specific, based on the ability to suppress a tumor-stimulated mixed lymphocyte response (MLR) and the related autologous MLR and an inability to suppress an allogeneic- or Con A-induced response. Since CD8 cells from CY treated mice had no demonstrable antitumor activity, the most likely suppressor targets were responder CD4 cells in the tumor-stimulated MLR. The results emphasize that the design of a treatment protocol can take advantage of the immunodependency of a tumor.