Macrophage-mediated, antibody-dependent destruction of tumor cells in DBA/2 mice: in vitro identification of an in situ mechanism.
A macrophage-mediated, antibody-dependent phagocytic mechanism of in situ tumor cell destruction was evident in the T1699 mammary adenocarcinoma model. The tumor-associated effector macrophages (TuM theta) required immune serum at low effector-to-target-cell ratios for rapid phagocytosis and destruction of cultured T1699 cells in vitro. Whereas TuM theta were inactive against such cultured T1699 cells, TuM theta rapidly engulfed and destroyed target cells isolated from the same tumor as the macrophages themselves. TuM theta containing intact and partially degraded tumor cells were both isolated from regressing tumors and identified in histologic sections. [3H]thymidine pulse-labeling studies of rergressing tumors in DBA/2 mice indicated that TuM theta phagocytosis of recently dividing tumor cells was common. This supports the concept that macrophage-mediated antibody-dependent tumor cell destruction, though not the only process involved in tumor regression, could be a potentially efficient and relevant mechanism for in vivo tumor cell destruction. Although the data do not formally prove that the phagocytosed tumor cells were undamaged prior to ingestion, the indication is that a particular class of macrophage was relevant in situ for tumor cell destruction either solely through phagocytosis or a combination of events. Inasmuch as TuM theta contained more than 10% of the tumor cells in regressing tumors, the importance of these macrophages to the process appeared relevant. These data also suggest that, inasmuch as phagocytosed intact tumor cells have a life-span of less than 2 hours, the infrequent description of this phenomenon in both experimental and clinical situations may be partly a result of difficulties in detection.
D000818:Animals; D000920:Antibody-Dependent Cell Cytotoxicity; D001345:Autoradiography; D002460:Cell Line; D002469:Cell Separation; D005260:Female; D006652:Histological Techniques; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008811:Mice, Inbred DBA; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000276:immunology*; D010587:Phagocytosis