CD271 on melanoma cell is an IFN-γ-inducible immunosuppressive factor that mediates downregulation of melanoma antigens.
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.
Department of Dermatology, University of Yamanashi, Chuo, Yamanashi, Japan.
Junpei
J
Furuta
Department of Dermatology, University of Yamanashi, Chuo, Yamanashi, Japan. Electronic address: tinozume@yamanashi.ac.jp.
Takashi
T
Inozume
Department of Dermatology, University of Yamanashi, Chuo, Yamanashi, Japan.
Kazutoshi
K
Harada
Department of Dermatology, University of Yamanashi, Chuo, Yamanashi, Japan.
Shinji
S
Shimada
D060890:B7-H1 Antigen / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism; D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000187:drug effects / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance / Q000187:drug effects / Q000502:physiology*; D007371:Interferon-gamma / Q000276:immunology* / Q000494:pharmacology; D058965:MART-1 Antigen / Q000378:metabolism; D008545:Melanoma / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D058950:Melanoma-Specific Antigens / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D017475:Receptors, Nerve Growth Factor / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D012878:Skin Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects / Q000276:immunology
D060890:B7-H1 Antigen; D014408:Biomarkers, Tumor; C423236:CD274 protein, human; D058965:MART-1 Antigen; C548667:MLANA protein, human; D058950:Melanoma-Specific Antigens; C484065:NGFR protein, human; D009419:Nerve Tissue Proteins; D017475:Receptors, Nerve Growth Factor; D007371:Interferon-gamma