CD271 on Melanoma Cell Is an IFN-γ-Inducible Immunosuppressive Factor that Mediates Downregulation of Melanoma Antigens

IFN-gamma released from cytotoxic T lymphocytes (CTLs) during the effector phase is essential for rejecting bulky melanoma tumors. In contrast, IFN-gamma 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-gamma-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.