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.