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Macrophage Processing of Antigen for Induction of Tumor Immunity¹

Department of Medical Microbiology, Stanford University School of Medicine, Stanford, California 94305

Previous studies have indicated, that, after in vitro incubation of antigen with macrophages, the "processed" antigen preferentially induces cell-mediated immunity. To investigate this phenomenon with tumor antigens, mycobacteria-stimulated macrophages were incubated with irradiated syngeneic EMT6 tumor cells for varying lengths of time and injected into normal mice. On subsequent challenge with EMT6, there was a significant increase in protection in mice immunized with macrophage-processed tumor antigen over control animals. Mineral oil-stimulated macrophages were also capable of processing irradiated EMT6, but macrophages induced by thioglycollate or proteose peptone were not. Freeze-thawed mycobacteria-stimulated macrophages were nearly as effective as viable macrophages in processing tumor antigen, but heat-treated macrophages lost this capacity. The immunity generated was specific and could be passively transferred by immune cells but not by immune serum. The results indicate that incubation of tumor antigen with appropriately activated macrophages leads to the enhanced induction of immunity to the tumor. Macrophage enzymes may degrade tumor antigens to fragments with few antigenic determinants that preferentially induce cell-mediated immunity.

¹ Supported by USPHS Grant AI-01178 and Training Grant AI-00082 awarded by the National Institute of Allergy and Infectious Diseases; also supported by the Fenton L. Tippett Allergy and Asthman Research Fund.

² Present address, Department of Medicine, Section of Allergy and Clinical Immunology, National Jewish Hospital and Research Center, Denver, Col. 80206. To whom requests for reprints should be addressed.

Received 1/19/77. Accepted 3/21/77.