ALTERATIONS IN THE TUMORICIDAL FUNCTIONS OF MURINE TUMOR-ASSOCIATED MACROPHAGES DURING PROGRESSIVE GROWTH OF A TUMOR IN-VIVO

Tumor cytolytic functions of tumor-associated macrophages (TAM) obtain ed from different of Dalton's lymphoma (DL, a spontaneous T cell lymph oma) were studied. DL-associated macrophages (DLAM) obtained in early tumor-bearing stages showed an augmented tumor cytotoxicity as well as an enhanced production of reactive nitrogen intermediates (RNI). Howe ver; these cytolytic functions declined at the later tumor-bearing sta ges. The effect of in vivo turner progression on the macrophage cytoly tic ie functions was simulated in vitro by incubating normal peritonea l macrophages (NMO) with different concentrations of DE cells. The NMO -mediated tumoricidal activity was inhibited in a DL-cell-number-depen dent manner, indicating that suppressive effectors originating from DL origin acted at a higher concentration, addition of anti-DL antiserum to these cultures reversed the DL-mediated alterations bf macrophage tumoricidal functions, confirming that this suppression was mediated b y the factors of DL-cell origin. The normal phenotype of DL cells (thy mocytes) could not mimic the inhibitory effects of DL on macrophage fu nctions. indicating that the macrophage-suppressive activity was a tum or-cell-restricted phenomenon. In-vivo administration of a synthetic a cyl tripeptide, FK565, could increase RNI production by DLAM only at e arly tumor-bearing stages, while the DLAM from later tumor-bearing sta ges were found to be nonresponsive to this activation. These observati ons should be helpful in understanding the effect of in vivo growth of a T-lymphoma on the functions of tumor-associated macrophages and the ir responsiveness to therapeutic manipulation by a biological response modifier.