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.
Prechel
M M
MM
Research Service, Hines VA Hospital, IL 60141, USA.
Lozano
Y
Y
Wright
M A
MA
Ihm
J
J
Young
M R
MR
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D018827:Carcinoma, Lewis Lung / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D006098:Granulocytes / Q000166:cytology / Q000276:immunology*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000276:immunology*; D007108:Immune Tolerance / Q000187:drug effects; D007111:Immunity, Cellular / Q000187:drug effects; D018664:Interleukin-12 / Q000494:pharmacology*; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D008264:Macrophages / Q000166:cytology / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000187:drug effects / Q000276:immunology
D000276:Adjuvants, Immunologic; D018664:Interleukin-12