The anti-tumor activity of IL-12: mechanisms of innate immunity that are model and dose dependent

J Immunol. 2000 Sep 1;165(5):2665-70. doi: 10.4049/jimmunol.165.5.2665.

Abstract

IL-12 has been demonstrated to have potent anti-tumor activities in a variety of mouse tumor models, but the relative roles of NK, NKT, and T cells and their effector mechanisms in these responses have not been fully addressed. Using a spectrum of gene-targeted or Ab-treated mice we have shown that for any particular tumor model the effector mechanisms downstream of IL-12 often mimic the natural immune response to that tumor. For example, metastasis of the MHC class I-deficient lymphoma, EL4-S3, was strictly controlled by NK cells using perforin either naturally or following therapy with high-dose IL-12. Intriguingly, in B16F10 and RM-1 tumor models both NK and NKT cells contribute to natural protection from tumor metastasis. In these models, a lower dose of IL-12 or delayed administration of IL-12 dictated a greater relative role of NKT cells in immune protection from tumor metastasis. Overall, both NK and NKT cells can contribute to natural and IL-12-induced immunity against tumors, and the relative role of each population is tumor and therapy dependent.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / therapeutic use
  • Disease Models, Animal*
  • Dose-Response Relationship, Immunologic
  • Drug Administration Schedule
  • Immunity, Innate / genetics
  • Injections, Intraperitoneal
  • Interferon-gamma / deficiency
  • Interferon-gamma / genetics
  • Interferon-gamma / physiology
  • Interleukin-12 / administration & dosage*
  • Interleukin-12 / physiology
  • Interleukin-12 / therapeutic use
  • Killer Cells, Natural / immunology
  • Lung Neoplasms / genetics
  • Lung Neoplasms / immunology
  • Lung Neoplasms / prevention & control
  • Lung Neoplasms / secondary
  • Lymphocyte Depletion
  • Lymphoma / immunology
  • Lymphoma / prevention & control
  • Male
  • Melanoma, Experimental / immunology
  • Melanoma, Experimental / prevention & control
  • Melanoma, Experimental / secondary
  • Membrane Glycoproteins / deficiency
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / physiology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neoplasm Transplantation
  • Perforin
  • Pore Forming Cytotoxic Proteins
  • Prostatic Neoplasms / immunology
  • Prostatic Neoplasms / prevention & control
  • T-Lymphocyte Subsets / immunology
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents
  • Membrane Glycoproteins
  • Pore Forming Cytotoxic Proteins
  • Perforin
  • Interleukin-12
  • Interferon-gamma