Potentiation of Antitumor CTL Response by GM-CSF Involves a B7-Dependent Mechanism

Abstract

We have previously demonstrated the importance of endogenous GM-CSF production for the B7-2-dependent potentiating effect of exogenous TNF for CTL generation by stimulation cultures of splenic cells from mice bearing a large MOPC-315 tumor. Here we show that addition of GM-CSF to stimulation cultures of such tumor-bearer splenic cells also leads to the generation of enhanced anti-MOPC-315 CTL activity via a B7-dependent mechanism. However, while the potentiating effect of TNF was previously shown to be IL-2-independent, the potentiating effect of GM-CSF is shown here to be completely IL-2-dependent. Still, the potentiating activity of exogenous GM-CSF for thein vitrogeneration of CTL activity is shown to depend completely on endogenous TNF production. Finally, TNF and GM-CSF may cooperate in enhancing thein vivogeneration of CTL activity in MOPC-315 tumor bearers because low-dose melphalan (l-phenylalanine mustard) therapy, which was previously shown to lead to the rapid up-regulation of TNF production at the tumor site and the subsequent TNF-dependentin vivoacquisition of potent CTL activity, is shown here to lead to the rapid up-regulation of GM-CSF production at the tumor site.