Epigenetic therapies for neuroblastoma: immunogenicity awakens

Abstract

The development of immunotherapies for neuroblastoma remains challenging owing to the low immunogenicity of neuroblastoma cells, as reflected by the low expression of one of the main triggers of immune recognition, the major histocompatibility complex class I (MHC-I). Cornel et al. showed that epigenetic modulation of neuroblastoma cells with a histone deacetylase inhibitor can boost the expression of major histocompatibility complex class I, among other immune receptors, priming their recognition by T- and natural killer cells. By leveraging the developmentally related aberrant epigenetic landscapes of neuroblastoma, these discoveries pave the way to overcome a major limitation in the field of neuroblastoma immunotherapy.

Keywords: histone deacetylase inhibitors; immunotherapy; major histocompatibility complex class I; neuroblastoma.

Fig. 1

Immunogenic activation of neuroblastoma cells through epigenetic therapy. Cornel et al. showed in their recent work that the expression of multiple immune system receptors, epigenetically silenced in neuroblastoma cells as a result of its developmental origins, can be restored with the histone deacetylase (HDAC) inhibitor entinostat. This epigenetic modulation boosts the expression of major histocompatibility complex class I (MHC‐I), key for T‐cell recognition, and human leukocyte antigen E (HLA‐E) and MHC class I chain‐related proteins A and B (MICA/B), receptors of natural killer (NK) cells, thereby triggering a cytotoxic immune response against neuroblastoma cells.