WSX1 expression in tumors induces immune tolerance via suppression of effector immune cells

PLoS One. 2011 Apr 29;6(4):e19072. doi: 10.1371/journal.pone.0019072.

Abstract

Crosstalk between tumor cells and the cognate microenvironment plays a crucial role in tumor initiation and progression. However, only a few genes are known to affect such a crosstalk. This study reveals that WSX1 plays such a role when highly expressed in tumor cells. The expression of WSX1 in Lewis Lung Carcinoma (LLC) and the melanoma cell line AGS induces the death of T cells and inhibits the production of the effector cytokine IFNγ from NK and T cells, resulting in the promotion of tumor growth. These pro-tumorigenic properties of WSX1 are independent of IL27. This key observation reveals a new pathway of tumor-host interaction, which will ultimately lead to better strategies in immune therapy to reverse tumor tolerance.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Carcinoma, Lewis Lung / immunology
  • Carcinoma, Lewis Lung / metabolism*
  • Cell Line, Tumor
  • Coculture Techniques
  • Cytokines / metabolism
  • Immune System
  • Immune Tolerance
  • Interferon-gamma / metabolism
  • Interleukin-17 / metabolism
  • Killer Cells, Natural / cytology
  • Melanoma / immunology
  • Melanoma / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Mice, SCID
  • Microscopy, Confocal / methods
  • Receptors, Cytokine / biosynthesis*
  • Receptors, Cytokine / physiology
  • Receptors, Interleukin
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology

Substances

  • Cytokines
  • Il27ra protein, mouse
  • Interleukin-17
  • Receptors, Cytokine
  • Receptors, Interleukin
  • Interferon-gamma