SUPPRESSION OF THE DELAYED-TYPE HYPERSENSITIVITY RESPONSE BY TUMOR FACILITATING FACTOR OF B16 MELANOMA - A TUMOR FACTOR SUPPRESSES IMMUNE-RESPONSES

BACKGROUND. Tumor facilitating factor is a cell surface glycoprotein p roduced by B16 melanoma that has been found to reduce the lethal inocu lum for B16. Tumor facilitating factor induces macrophage spreading in vitro, reduces macrophage chemotaxis in vivo, and depresses lymphocyt e mitogenesis in vitro. OBJECTIVE. It is assumed that the immune modif ying effects are responsible for tumor facilitation. As tumors may be poor immunogens or inducers of inflammation, studies were conducted to determine whether tumor facilitating factor alters the inflammatory c ascade of cells found in infiltrates of delayed type hypersensitivity. RESULTS. Freeze-thawed B16 cells, used as the source of TFF, caused a suppression of delayed type hypersensitivity measured as ear swelling in the mouse. When culture supernatant was substituted for freeze-tha wed cells as a source of TFF and injected at different time points of the delayed type hypersensitivity response, the greater suppression wa s with tumor facilitating factor injections at 24 hours pre-elicitatio n only (82%), and 24 hours both presensitization and pre-elicitation ( 89%). Immunohistological staining demonstrated that tumor facilitating factor decreases ear thickness and cellular infiltrates, specifically Mac-1 staining cells, to a site of delayed hypersensitivity. Peritone al cell analysis confirmed these findings. CONCLUSION. These data are consistent with the hypothesis that tumor facilitating factor alters i mmune functions including macrophage and lymphocyte mobility and recru itment to a target site, thereby allowing for facilitation of tumor gr owth.