Natural killer cells efficiently reject lymphoma silenced for the endoplasmic reticulum aminopeptidase associated with antigen processing |
| |
Authors: | Cifaldi Loredana Lo Monaco Elisa Forloni Matteo Giorda Ezio Lorenzi Silvia Petrini Stefania Tremante Elisa Pende Daniela Locatelli Franco Giacomini Patrizio Fruci Doriana |
| |
Institution: | Oncohaematology Department, IRCCS, Ospedale Pediatrico Bambino Gesù, Rome, Italy. |
| |
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. |
| |
Keywords: | |
本文献已被 PubMed 等数据库收录! |
|