Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 1 de 1
Filtrar
Mais filtros

Base de dados
Ano de publicação
Tipo de documento
Intervalo de ano de publicação
1.
Haematologica ; 107(12): 2905-2917, 2022 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-35263985

RESUMO

Aggressive B-cell malignancies, such as mantle cell lymphoma (MCL), are microenvironment-dependent tumors and a better understanding of the dialogs occurring in lymphoma-protective ecosystems will provide new perspectives to increase treatment efficiency. To identify novel molecular regulations, we performed a transcriptomic analysis based on the comparison of circulating MCL cells (n=77) versus MCL lymph nodes (n=107) together with RNA sequencing of malignant (n=8) versus normal B-cell (n=6) samples. This integrated analysis led to the discovery of microenvironment-dependent and tumor-specific secretion of interleukin-32 beta (IL32ß), whose expression was confirmed in situ within MCL lymph nodes by multiplex immunohistochemistry. Using ex vivo models of primary MCL cells (n=23), we demonstrated that, through the secretion of IL32ß, the tumor was able to polarize monocytes into specific MCL-associated macrophages, which in turn favor tumor survival. We highlighted that while IL32ß-stimulated macrophages secreted several protumoral factors, they supported tumor survival through a soluble dialog, mostly driven by BAFF. Finally, we demonstrated the efficacy of selective NIK/alternative-NFkB inhibition to counteract microenvironment-dependent induction of IL32ß and BAFF-dependent survival of MCL cells. These data uncovered the IL32ß/BAFF axis as a previously undescribed pathway involved in lymphoma-associated macrophage polarization and tumor survival, which could be counteracted through selective NIK inhibition.


Assuntos
Fator Ativador de Células B , Interleucinas , Linfoma de Célula do Manto , Proteínas Serina-Treonina Quinases , Adulto , Humanos , Linhagem Celular Tumoral , Interleucinas/metabolismo , Linfoma de Célula do Manto/patologia , Macrófagos/metabolismo , NF-kappa B/metabolismo , Microambiente Tumoral , Fator Ativador de Células B/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Quinase Induzida por NF-kappaB
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA