The responses of splenocytes from normal and mammary tumor bearing Balb/c mice were assessed following treatment with cyclophosphamide in several immune reactions which may be important correlates of antitumor immunity. Although this drug is in common use as a treatment of many neoplasias including breast cancer, its effects on the lymphoid cells responding to tumor antigens have not been clearly elucidated. Administration of 100 mg/kg body weight of the drug two days prior to testing severely suppressed the lymphoproliferative and cytotoxic responses elicited by tumor associated antigens in mammary tumor bearing mice. Likewise, blastogenic responses to B and T cell mitogens were severely impaired. In sharp contrast, an equivalent dose of cyclosphosphamide did not affect either antibody dependent cellular cytotoxicity (ADCC) or lectin-induced cytotoxicity. When 200 mg/kg body weight was administered, the levels of phytohemagglutinin (PHA)-induced cytotoxicity were greatly reduced in both normal and tumor bearers, however, ADCC remained unaffected. Flow cytometric studies of cell surface markers determined that both Thy 1.2 positive and more profoundly, surface immunoglobulin bearing cells were diminished by cyclophosphamide treatment. The results suggest that the lymphoid cells which respond to tumor associated antigens, in PHA-induced cytotoxicity and in ADCC have qualitatively and quantitatively different susceptibilities to cyclophosphamide. These observations may help explain the chemotherapeutic effectiveness of cyclophosphamide in spite of its immunosuppressive properties.
|Number of pages||8|
|State||Published - Dec 1 1982|
ASJC Scopus subject areas
- Cancer Research