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Sci Adv ; 10(19): eadm7515, 2024 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-38728394

RESUMEN

The nonpolymorphic major histocompatibility complex E (MHC-E) molecule is up-regulated on many cancer cells, thus contributing to immune evasion by engaging inhibitory NKG2A/CD94 receptors on NK cells and tumor-infiltrating T cells. To investigate whether MHC-E expression by cancer cells can be targeted for MHC-E-restricted T cell control, we immunized rhesus macaques (RM) with rhesus cytomegalovirus (RhCMV) vectors genetically programmed to elicit MHC-E-restricted CD8+ T cells and to express established tumor-associated antigens (TAAs) including prostatic acidic phosphatase (PAP), Wilms tumor-1 protein, or Mesothelin. T cell responses to all three tumor antigens were comparable to viral antigen-specific responses with respect to frequency, duration, phenotype, epitope density, and MHC restriction. Thus, CMV-vectored cancer vaccines can bypass central tolerance by eliciting T cells to noncanonical epitopes. We further demonstrate that PAP-specific, MHC-E-restricted CD8+ T cells from RhCMV/PAP-immunized RM respond to PAP-expressing HLA-E+ prostate cancer cells, suggesting that the HLA-E/NKG2A immune checkpoint can be exploited for CD8+ T cell-based immunotherapies.


Asunto(s)
Antígenos de Neoplasias , Linfocitos T CD8-positivos , Antígenos HLA-E , Animales , Humanos , Masculino , Fosfatasa Ácida , Presentación de Antígeno/inmunología , Antígenos de Neoplasias/inmunología , Vacunas contra el Cáncer/inmunología , Linfocitos T CD8-positivos/inmunología , Línea Celular Tumoral , Citomegalovirus/inmunología , Antígenos de Histocompatibilidad Clase I/inmunología , Antígenos de Histocompatibilidad Clase I/metabolismo , Macaca mulatta , Mesotelina
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