Effect of cyclophosphamide on mice bearing methylcholanthrene-induced fibrosarcomas.

Mice bearing large methylcholanthrene-induced fibrosarcomas lost the ability to respond in vitro to mitogen stimulation and to specifically neutralize autologous tumor cells in vivo. This depressed immune capability was due to active suppression, since spleen cells from advanced tumor-bearing mice could suppress the mitogen response of normal spleen cells and could inhibit tumor rejection when adoptively transferred to mice previously immunized against the tumor. Treatment with cyclophosphamide (CY) was found to affect the immune capability of the host, in addition to have a direct effect on the tumor. The number of cells in the lymph nodes and spleen, as well as their response to concanavalin A and lipopolysaccharide (but not phytohemagglutinin), decreased initially but returned to normal by Day 14. Most importantly, when CY was administered one day after tumor inoculation, the treated animals developed the ability to neutralize tumor at the same time as untreated controls but retained this capability as the tumors became advanced. Treatment with a single dose of CY as late as 11 or 20 days after tumor inoculation maintained or restored the tumor-neutralizing capacity of spleen cells. CY appears to alter the antitumor response of the host by inhibiting both cytotoxic and suppressor cells, but the cytotoxic cells recover rapidly, whereas the suppressor cells do not.