Melanoma cells express ICOS ligand to promote the activation and expansion of T-regulatory cells

Cancer Res. 2010 Dec 1;70(23):9581-90. doi: 10.1158/0008-5472.CAN-10-1379. Epub 2010 Nov 23.

Abstract

CD4(+)CD25(+)Foxp3(+) T-regulatory cells (Tregs) accumulate in tumors; however, little is known about how the tumor environment influences this process. Here we show that human melanomas express inducible T-cell costimulator ligand (ICOS-L/B7H) that can provide costimulation through ICOS for the expansion of activated Tregs maintaining high Foxp3 and CD25 expression as well as a suppressive function. Thus, ICOS-L expression by melanoma tumor cells may directly drive Treg activation and expansion in the tumor microenvironment as another mechanism of immune evasion.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD / genetics
  • Antigens, CD / metabolism*
  • Cell Line, Tumor
  • Cell Proliferation*
  • Coculture Techniques
  • Flow Cytometry
  • Forkhead Transcription Factors / metabolism
  • Humans
  • Inducible T-Cell Co-Stimulator Ligand
  • Interferon-gamma / metabolism
  • Interleukin-10 / metabolism
  • Interleukin-2 Receptor alpha Subunit / metabolism
  • L Cells
  • Lymphocyte Activation / immunology
  • Melanoma / genetics
  • Melanoma / metabolism*
  • Melanoma / pathology
  • Melanoma, Experimental / genetics
  • Melanoma, Experimental / metabolism
  • Melanoma, Experimental / pathology
  • Mice
  • Mice, Inbred C57BL
  • Reverse Transcriptase Polymerase Chain Reaction
  • T-Lymphocytes, Regulatory / immunology
  • T-Lymphocytes, Regulatory / metabolism*
  • Tumor Microenvironment

Substances

  • Antigens, CD
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • ICOSLG protein, human
  • Inducible T-Cell Co-Stimulator Ligand
  • Interleukin-2 Receptor alpha Subunit
  • Interleukin-10
  • Interferon-gamma