Enhanced stimulation of antigen-specific immune responses against nucleophosmin 1 mutated acute myeloid leukaemia by an anti-programmed death 1 antibody.
Br J Haematol
; 198(5): 866-874, 2022 09.
Article
en En
| MEDLINE
| ID: mdl-35799423
ABSTRACT
Nucleophosmin1 (NPM1) is one of the most commonly mutated genes in AML and is often associated with a favourable prognosis. Immune responses play an increasing role in AML treatment decisions; however, the role of immune checkpoint inhibition is still not clear. To address this, we investigated specific immune responses against NPM1, and three other leukaemia-associated antigens (LAA), PRAME, Wilms' tumour 1 and RHAMM in AML patients. We investigated T cell responses against leukaemic progenitor/stem cells (LPC/LSC) using colony-forming immunoassays and flow cytometry. We examined whether immune checkpoint inhibition with the anti-programmed death 1 antibody increases the immune response against stem cell-like cells, comparing cells from NPM1 mutated and NPM1 wild-type AML patients. We found that the anti-PD-1 antibody, nivolumab, increases LAA stimulated cytotoxic T lymphocytes and the cytotoxic effect against LPC/LSC. The effect was strongest against NPM1mut cells when the immunogenic epitope was derived from the mutated region of NPM1 and these effects were enhanced through the addition of anti-PD-1. The data suggest that patients with NPM1 mutated AML could be treated with the immune checkpoint inhibitor anti-PD-1 and that this treatment combined with NPM1-mutation specific directed immunotherapy could be even more effective for this unique group of patients.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Linfocitos T Citotóxicos
/
Leucemia Mieloide Aguda
/
Inhibidores de Puntos de Control Inmunológico
/
Nucleofosmina
Límite:
Humans
Idioma:
En
Revista:
Br J Haematol
Año:
2022
Tipo del documento:
Article
País de afiliación:
Alemania