Natural killer cells efficiently reject lymphoma silenced for the endoplasmic reticulum aminopeptidase associated with antigen processing

Loredana Cifaldi, Elisa Lo Monaco, Matteo Forloni, Ezio Giorda, Silvia Lorenzi, Stefania Petrini, Elisa Tremante, Daniela Pende, Franco Locatelli, Patrizio Giacomini, Doriana Fruci

Research output: Contribution to journalArticlepeer-review

Abstract

The endoplasmic reticulum aminopeptidase ERAAP is involved in the final trimming of peptides for presentation by MHC class I (MHC-I) molecules. Herein, we show that ERAAP silencing results in MHC-I peptide-loading defects eliciting rejection of the murine T-cell lymphoma RMA in syngeneic mice. Although CD4 and CD8 T cells are also involved, rejection is mainly due to an immediate natural killer (NK) cell response and depends on the MHC-I-peptide repertoire because replacement of endogenous peptides with correctly trimmed, high-affinity peptides is sufficient to restore an NK-protective effect of MHC-I molecules through the Ly49C/I NK inhibitory receptors. At the crossroad between innate and adaptive immunity, ERAAP is therefore unique in its two-tiered ability to control tumor immunogenicity. Because a large fraction of human tumors express high levels of the homologous ERAP1 and/or ERAP2, the present findings highlight a convenient, novel target for cancer immunotherapy.

Original languageEnglish
Pages (from-to)1597-1606
Number of pages10
JournalCancer Research
Volume71
Issue number5
DOIs
Publication statusPublished - Mar 1 2011

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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