Role of antitumor immunity in cyclophosphamide-induced rejection of subcutaneous nonpalpable MOPC-315 tumors.

Previously, we had reported that a single i.p. injection of 15 mg cyclophosphamide (CY) per kg cured most mice bearing large MOPC-315 tumors (20 to 25 mm; Day 12 to Day 16 tumors) but rarely cured mice bearing nonpalpable tumors (Day 4 tumors). Also, mice that were not cured if treated with CY, 15 mg/kg, when they had nonpalpable tumors could not be cured if treated again with CY, 15 mg/kg, when they had large tumors (14). Here, we show that CY therapy with 15 mg/kg at early stages of tumor growth did not lead to alteration in the biology of the tumor so as to cause an increased resistance to CY-tumoricidal effects, increased resistance to immune lysis, and/or decreased immunogenicity. Treatment of nonpalpable tumor bearers with CY, 15 mg/kg, prior to in vitro immunization of their spleen cells did not reduce the ability of the spleen cells to generate antitumor cytotoxicity in vitro. However, the level of antitumor cytotoxicity generated was lower than that exhibited by in vitro-immunized spleen cells from mice treated with CY, 15 mg/kg, when they had large tumors. With CY, 15 mg/kg, mice bearing nonpalpable tumors could be cured in two ways: (a) by treating a mouse bearing a nonpalpable tumor in the presence of a contralateral large tumor; (b) by adoptive transfer of immune spleen cells given 1 day post-CY therapy. Both procedures resulted in higher levels of antitumor immunity which was apparently responsible for the cure of the mice in cooperation with CY. Thus, the ineffectiveness of CY therapy with 15 mg/kg at early stages of tumor growth correlated with the presence of relatively low levels of host antitumor immunity.