CD271 on melanoma cell is an IFN-γ-inducible immunosuppressive factor that mediates downregulation of melanoma antigens

J Invest Dermatol. 2014 May;134(5):1369-1377. doi: 10.1038/jid.2013.490. Epub 2013 Nov 13.


IFN-γ released from cytotoxic T lymphocytes (CTLs) during the effector phase is essential for rejecting bulky melanoma tumors. In contrast, IFN-γ is known to induce certain immunosuppressive factors in tumor cells such as programmed cell death 1 ligand 1 (PD-L1). In this study, we have identified candidates for IFN-γ-inducible CTL-suppressive factors in melanoma cells using complementary DNA microarray analysis, and CD271/p75/neurotrophin receptor (NTR) was one of the candidate genes. Recently, CD271 was identified as a marker of the cancer stem cell-like population in human melanoma tissues. In this study, we showed that overexpression of CD271 on melanoma cells suppressed the in vitro activation of melanoma-specific CTLs. This suppression was mediated by CD271 ligation with activated CTL-derived nerve growth factor and the subsequent downregulation of melanoma antigens. Moreover, we found that the expression levels of PD-L1 on melanoma cells correlated with those of CD271, and they additively suppressed the activation of melanoma-specific CTLs. To the best of our knowledge, the role of overexpression of CD271 in an anti-melanoma T-cell response has been unreported.

MeSH terms

  • B7-H1 Antigen / metabolism
  • Biomarkers, Tumor / metabolism
  • Cell Line, Tumor
  • Down-Regulation / drug effects
  • Down-Regulation / immunology
  • Humans
  • Immune Tolerance / drug effects
  • Immune Tolerance / physiology*
  • Interferon-gamma / immunology*
  • Interferon-gamma / pharmacology
  • MART-1 Antigen / metabolism
  • Melanoma / immunology*
  • Melanoma / metabolism
  • Melanoma / pathology
  • Melanoma-Specific Antigens / genetics
  • Melanoma-Specific Antigens / immunology
  • Melanoma-Specific Antigens / metabolism
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / immunology*
  • Nerve Tissue Proteins / metabolism
  • Oligonucleotide Array Sequence Analysis
  • Receptors, Nerve Growth Factor / genetics
  • Receptors, Nerve Growth Factor / immunology*
  • Receptors, Nerve Growth Factor / metabolism
  • Skin Neoplasms / immunology*
  • Skin Neoplasms / metabolism
  • Skin Neoplasms / pathology
  • T-Lymphocytes, Cytotoxic / immunology*
  • T-Lymphocytes, Cytotoxic / metabolism
  • Up-Regulation / drug effects
  • Up-Regulation / immunology


  • B7-H1 Antigen
  • Biomarkers, Tumor
  • CD274 protein, human
  • MART-1 Antigen
  • MLANA protein, human
  • Melanoma-Specific Antigens
  • NGFR protein, human
  • Nerve Tissue Proteins
  • Receptors, Nerve Growth Factor
  • Interferon-gamma