[Studies on the immuno-suppressive effects of adriamycin and tumor metastasis (author's transl)]

Most of the antineoplastic agents were known to have immuno-suppressive effect. The purpose of the present work is to test the immuno-suppressive effect of adriamycin, an effective and widely used chemotherapeutic agent in the field of clinical orthopedics. Isogenic ACI rats and their transplantable fibrosarcoma AMC-60 were used as test materials. Tumor cells were injected as an artificial model for pulmonary metastasis or inoculated into the tibial bone to examine any metastatic focus other than the inoculated site. Administration of one course of adriamycin in the same way as that was given in patients induced temporarily leucopenia with prominent decrease of granulocytes. Adriamycin suppressed humoral antibody production to sheep erythrocytes in the treated rats and also suppressed cellular immune response expressed by skin reaction to PHA in the treated rats. Administration of adriamycin one week before tumor inoculation into immune rats which have acquired immunity to AMC-60 through preimmunization with the tumor, induced increased incidence of pulmonary metastasis, whereas administration of adriamycin after tumor inoculation resulted in decreased incidence of metastasis or healing of the inoculated tumor. Inoculation of bone marrow cells from healthy rats restored the impaired immunity. In unimmunized rats, pretreatment by adriamycin resulted in accelerated tumor growth at the inoculated site and increased incidence of metastasis. On the other hand, adriamycin given after tumor inoculation suppressed tumor growth and repeated administration of adriamycin induced healing of the inoculated tumor. The present data indicates that even an effective antineoplastic agent will interfere with the immune surveillance system of the host and result in accelerated tumor growth or increased incidence of metastasis when improperly given. A continual efforts to search for a less immuno-suppressive and effective method of administration of a given antineoplastic agent is necessary.