DESCRIPTION: The objective of these studies is to carry out further investigations of the mechanisms underlying the induction of anti-tumor immune responses following interactions between macrophages and tumor cell bearing the membrane form of macrophage colony stimulating factor (mM- CSF). In previous work, the applicants have shown that tumor cells selectively expressing mM-CSF (but not soluble CSF), when implanted in rat brains, are rejected and generated a (presumed) T-cell dependent immune response followed by resistance to challenge with the parental T9 glioma cell line. The observations indicate that mM-CSF transfection leads to both direct tumor rejection and long-term immunity against the parental tumor. The central hypothesis is that macrophages first kill mM-CSF expressing tumor cells through a poorly understood mechanism. The mM-CSF activated macrophages which have phagocytosed the tumor cells then act as antigen presenting cells, stimulating a T-cell dependent immune response and subsequent immunity to the mechanism(s) through which macrophages mediate such anti-tumor responses. The specific aims are (1) identification of gene products induced within macrophages responding to mM-CSF, using polymerase chain reaction and differential display; (2) cloning and sequencing of selected genes to determine their identify and whether they are unique; and (3) determining whether these gene products play an integral role in the mM-CSF based reactions. The long term goal is to use a similar approach to make tumor cells more immunogenic and thereby stimulate cellular immunity against cancer in humans.