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

Cancer Lett. 1995 Jun 8;92(2):235-42. doi: 10.1016/0304-3835(95)03804-6.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adjuvants, Immunologic / pharmacology*
  • Animals
  • Carcinoma, Lewis Lung / drug therapy*
  • Carcinoma, Lewis Lung / immunology*
  • Carcinoma, Lewis Lung / pathology
  • Cell Division / drug effects
  • Granulocytes / cytology
  • Granulocytes / immunology*
  • Hematopoietic Stem Cells / cytology
  • Hematopoietic Stem Cells / immunology*
  • Immune Tolerance / drug effects
  • Immunity, Cellular / drug effects
  • Interleukin-12 / pharmacology*
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / immunology*
  • Lung Neoplasms / pathology
  • Macrophages / cytology
  • Macrophages / immunology*
  • Mice
  • Mice, Inbred C57BL
  • T-Lymphocytes / cytology
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology
  • T-Lymphocytes, Regulatory / cytology
  • T-Lymphocytes, Regulatory / drug effects
  • T-Lymphocytes, Regulatory / immunology

Substances

  • Adjuvants, Immunologic
  • Interleukin-12