Tumor growth changes the contribution of granulocyte-macrophage colony-stimulating factor during macrophage-mediated suppression of allorecognition

Abstract

Tumor-bearing host (TBH) macrophages (MΦ) suppress T cell alloresponses, and this study suggests granulocyte-macrophage colony-stimulating factor (GM-CSF), a molecule associated with suppressive MΦ activity during tumor growth, signals more immunosuppression. In the absence of MΦ, GM-CSF increased T cell proliferation in response to alloantigen. However, TBH MΦ-mediated suppression of allorecognition was further induced by GM-CSF. Allogeneic mixed lymphocyte reaction (MLR) cultures, containing normal host (NH) MΦ, were either unaffected or enhanced. Prostaglandin E2 (PGE 2), a highly suppressive monokine that decreases alloreactivity, did not seem to be involved in the suppression caused by the TBH MΦ/GM-CSF interaction. MΦ-CSF (M-CSF) addition to cultures did not reverse the suppression caused by TBH MΦ and GM-CSF, and inhibition of PGE 2 synthesis did not change the response to M-CSF. TBH 1a - MΦ, a suppressor population that predominates among splenic MΦ during tumor growth, demonstrated significantly lower reactivity in the presence of GM-CSF. In contrast, alloresponses suppressed by NH la - MΦ demonstrated higher reactivity in the presence of GM-CSF. The data collectively suggest that TBH MΦ respond differently to GM-CSF, and that tumor-induced changes in GM-CSF responsiveness affect MΦ accessory ability.