Host immune potentiation of drug responses to a murine mammary adenocarcinoma. II. Effect of melphalan therapy on the host immune system.

The role of chemotherapy in influencing tumor-specific immunity to a mouse mammary adenocarcinoma was investigated. By studying different stages of tumor growth we were able to identify several factors important to drug-induced tumor regression: (1) antibody response, (2) delayed hypersensitivity, (3) sensitivity of tumor cells to immune attack and (4) tumor burden. The presence of tumor-specific delayed hypersensitivity and circulating antibody as well as specifically armed monocytes in the tumor mass characterize the T1699 adenocarcinoma. Successful chemotherapy had previously been shown to depend on prior establishment of the above immune responses. Treatment with alkylating agents was marked in all animals by abrogation of a humoral response to the tumor when drug was given early (day 7), and was associated with poor chemotherapeutic results. Later treatment (day 10) was associated with depression of antibody titers only in the minority of animals not responding to drug and prolongation of the delayed hypersensitivity response in all treated animals. Tumors recurring following initial drug-induced regression were marked by lack of delayed hypersensitivity in the host, lack of drug response and suppression of humoral immunity following treatment. Successive passage of cells from these resistant tumors led to decreasing sensitivity to chemotherapy despite established immunity on the part of the host. The selection of tumor cells resistant to immune destruction rather than drug resistance per se appeared to pay a role. Melphalan was thus able to affect both favorably and adversely the immune factors important to drug-induced regression.