Ineffective immune enhancement by IL-12 in tumor-bearing mice whose immune depression is mediated by suppressive granulocyte-macrophage progenitor cells.

Lewis lung carcinoma (LLC-LN7) tumors stimulate myelopoiesis and induce immunosuppressive granulocyte-macrophage (GM)-progenitor cells. Treating mice having palpable tumors with IL-12 enhanced the frequency of GM-progenitors and did not diminish GM-suppressor activity. Proliferation of splenic T-cells of tumor-bearers to Con-A or to anti-CD3 plus IL-2 was suppressed; this was not enhanced by IL-12 treatment. Also not stimulated was T-cell secretion of IL-2 in response to autologous tumor, or the intratumoral T-cell content. IL-12 slightly increased splenic IFN-gamma secretion, and increased cytotoxicity of lymph node (but not spleen) cells toward autologous tumor. In these tumor-bearing mice that were immune depressed as a result of GM-suppressor cells, immune modulatory effects of IL-12 were marginal and did not affect tumor size or metastasis.