Collaboration between specific anti-tumor immunity and chemotherapeutic agents.
Treatment of DBA/2J mice bearing a T1699 syngeneic mammary adenocarcinoma (Ts) with a single intraperitoneal (i.p.) injection of 100 ug melphalan produced complete tumor regression in about 65% of the animals treated; however, tumors recurred in about 85% of these regressors after 15-25 days' remission. The drug regimen was ineffective against Ts tumors growing in immunosuppressed or immunodeficient animals. Stimulation of immunologically intact Ts tumor-bearers with bacterial lipopolysaccharide (LPS) or with phytohemagglutinin (PHA) 3 days prior to melphalan therapy, on the other hand, produced not only higher rates of tumor regression but also significant increases in the number of permanent cures. A tumor induced by T1699 subline TR2 was resistant to the same regimen, although Ts and TR2 cells were equally susceptible to the cytotoxic and growth-inhibiting activities of the drug in vitro. In contrast, the combination of specifically armed monocytes and melphalan in vitro produced enhanced killing of Ts cells but not of TR2 cells. Analysis of the collaborative cytotoxicity between immune effector cells and melphalan indicated that exposure of tumor cells to killer cells increased the drug susceptibility of the tumor cells, but not the reverse. These results suggest a possible mechanism for in vivo resistance of tumors to chemotherapeutic agents that is not directly associated with the drug resistance of the tumor cells in vitro.
D000230:Adenocarcinoma / Q000276:immunology*; D000276:Adjuvants, Immunologic / Q000627:therapeutic use; D000818:Animals; D003601:Cytotoxicity Tests, Immunologic; D004351:Drug Resistance; D005260:Female; D008070:Lipopolysaccharides / Q000627:therapeutic use; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy / Q000276:immunology*; D008558:Melphalan / Q000627:therapeutic use*; D051379:Mice; D009000:Monocytes / Q000276:immunology; D010835:Phytohemagglutinins / Q000627:therapeutic use; D013601:T-Lymphocytes / Q000276:immunology
D000276:Adjuvants, Immunologic; D008070:Lipopolysaccharides; D010835:Phytohemagglutinins; D008558:Melphalan