Infiltration of alternatively activated macrophages in cancer tissue is associated with MDSC and Th2 polarization in patients with esophageal cancer

PLoS One. 2014 Aug 21;9(8):e104453. doi: 10.1371/journal.pone.0104453. eCollection 2014.

Abstract

Myeloid derived suppressor cells (MDSCs) expand in cancer bearing hosts and contribute to tumor immune evasion. M2 macrophages constitute a major cellular component of cancer-related inflammation. However, the correlation between circulating MDSCs and infiltrating M2 macrophages in tumor tissues from patients with esophageal cancer (ECA), and its potential relationship with the polarization of Th2 cells remain unclear. In the present study, we showed the level of MDSCs in PBMC and Arg1 in plasma were significantly elevated in ECA patients, and the increased ratio of MDSC in PBMC was closely related to the expression of CD163 in cancer tissues. In addition, the ECA patients exhibited remarkable increases in the mRNA levels of IL-4 and GATA3, as well as the protein levels of IL-13 and IL-6, but IFN-γ and IL-12 in peripheral blood were decreased. Our data indicate that the increased Th2 cytokines are associated with MDSCs and M2 macrophages polarization, and foster the infiltration of CD163+M2 macrophages in cancer tissues, which promote the formation of immunosuppressive microenvironment in ECA patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Polarity / genetics
  • Cell Polarity / physiology
  • Cell Proliferation / physiology
  • Esophageal Neoplasms / immunology*
  • Esophageal Neoplasms / metabolism*
  • Female
  • Humans
  • Interferon-gamma / metabolism
  • Interleukin-12 / metabolism
  • Interleukin-13 / metabolism
  • Interleukin-6 / metabolism
  • Leukocytes, Mononuclear / metabolism
  • Macrophages / cytology*
  • Macrophages / metabolism*
  • Male
  • Middle Aged
  • Myeloid Cells / cytology*
  • Myeloid Cells / metabolism
  • Real-Time Polymerase Chain Reaction
  • Th2 Cells / cytology*
  • Th2 Cells / metabolism

Substances

  • Interleukin-13
  • Interleukin-6
  • Interleukin-12
  • Interferon-gamma

Grants and funding

This work was supported by grants from the National Natural Science Foundation of China (31270947, 31170849 and 30972748, http://www.nsfc.gov.cn/), Natural Science Foundation of Jiangsu Province (BK2011472) and the Postdoctoral Foundation of China (2012M511705). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.