Synergy between T-cell immunity and inhibition of paracrine stimulation causes tumor rejection

Proc Natl Acad Sci U S A. 1995 Jul 3;92(14):6254-8. doi: 10.1073/pnas.92.14.6254.

Abstract

During tumor progression, variants may arise that grow more vigorously. The fate of such variants depends upon the balance between aggressiveness of the variant and the strength of the host immunity. Although enhancing host immunity to cancer is a logical objective, eliminating host factors necessary for aggressive growth of the variant should also be considered. The present study illustrates this concept in the model of a spontaneously occurring, progressively growing variant of an ultraviolet light-induced tumor. The variant produces chemotactic factors that attract host leukocytes and is stimulated in vitro by defined growth factors that can be produced or induced by leukocytes. This study also shows that CD8+ T-cell immunity reduces the rate of tumor growth; however, the variant continues to grow and kills the host. Treatment with a monoclonal anti-granulocyte antibody that counteracts the infiltration of the tumor cell inoculum by non-T-cell leukocytes did not interfere with the CD8+ T-cell-mediated immune response but resulted in rejection of the tumor challenge, indicating a synergy between CD8+ T-cell-mediated immunity and the inhibition of paracrine stimulation.

Publication types

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

MeSH terms

  • Animals
  • Ascitic Fluid / immunology
  • Bone Marrow / immunology
  • Bone Marrow / pathology
  • CD8-Positive T-Lymphocytes / immunology
  • Cytotoxicity, Immunologic
  • Genetic Variation
  • Growth Substances / biosynthesis
  • Growth Substances / physiology
  • Immunity, Cellular
  • Leukocytes / immunology
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Lymphocytes, Tumor-Infiltrating / pathology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C3H
  • Mice, Nude
  • Neoplasms, Radiation-Induced / immunology*
  • Neoplasms, Radiation-Induced / pathology
  • T-Lymphocytes / immunology*
  • T-Lymphocytes, Cytotoxic / immunology*
  • Time Factors
  • Tumor Cells, Cultured
  • Ultraviolet Rays

Substances

  • Growth Substances