Interleukin-10 production by tumor infiltrating macrophages plays a role in Human Papillomavirus 16 tumor growth

BMC Immunol. 2010 Jun 7;11:27. doi: 10.1186/1471-2172-11-27.

Abstract

Background: Human Papillomavirus, HPV, is the main etiological factor for cervical cancer. Different studies show that in women infected with HPV there is a positive correlation between lesion grade and number of infiltrating macrophages, as well as with IL-10 higher expression. Using a HPV16 associated tumor model in mice, TC-1, our laboratory has demonstrated that tumor infiltrating macrophages are M2-like, induce T cell regulatory phenotype and play an important role in tumor growth. M2 macrophages secrete several cytokines, among them IL-10, which has been shown to play a role in T cell suppression by tumor macrophages in other tumor models. In this work, we sought to establish if IL-10 is part of the mechanism by which HPV tumor associated macrophages induce T cell regulatory phenotype, inhibiting anti-tumor activity and facilitating tumor growth.

Results: TC-1 tumor cells do not express or respond to IL-10, but recruit leukocytes which, within the tumor environment, produce this cytokine. Using IL-10 deficient mice or blocking IL-10 signaling with neutralizing antibodies, we observed a significant reduction in tumor growth, an increase in tumor infiltration by HPV16 E7 specific CD8 lymphocytes, including a population positive for Granzyme B and Perforin expression, and a decrease in the percentage of HPV specific regulatory T cells in the lymph nodes.

Conclusions: Our data shows that in the HPV16 TC-1 tumor mouse model, IL-10 produced by tumor macrophages induce regulatory phenotype on T cells, an immune escape mechanism that facilitates tumor growth. Our results point to a possible mechanism behind the epidemiologic data that correlates higher IL-10 expression with risk of cervical cancer development in HPV infected women.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Neutralizing / immunology
  • Antigens, Neoplasm / immunology
  • Cell Cycle
  • Cell Movement*
  • Cell Proliferation
  • Human papillomavirus 16 / immunology*
  • Humans
  • Interleukin-10 / biosynthesis*
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Macrophages / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Neoplasms / immunology
  • Neoplasms / pathology*
  • Neoplasms / virology*
  • Phenotype
  • Signal Transduction / immunology
  • T-Lymphocytes / immunology
  • T-Lymphocytes, Regulatory / immunology

Substances

  • Antibodies, Neutralizing
  • Antigens, Neoplasm
  • Interleukin-10