A blueprint for tumor-infiltrating B cells across human cancers.
Science
; 384(6695): eadj4857, 2024 May 03.
Article
em En
| MEDLINE
| ID: mdl-38696569
ABSTRACT
B lymphocytes are essential mediators of humoral immunity and play multiple roles in human cancer. To decode the functions of tumor-infiltrating B cells, we generated a B cell blueprint encompassing single-cell transcriptome, B cell-receptor repertoire, and chromatin accessibility data across 20 different cancer types (477 samples, 269 patients). B cells harbored extraordinary heterogeneity and comprised 15 subsets, which could be grouped into two independent developmental paths (extrafollicular versus germinal center). Tumor types grouped into the extrafollicular pathway were linked with worse clinical outcomes and resistance to immunotherapy. The dysfunctional extrafollicular program was associated with glutamine-derived metabolites through epigenetic-metabolic cross-talk, which promoted a T cell-driven immunosuppressive program. These data suggest an intratumor B cell balance between extrafollicular and germinal-center responses and suggest that humoral immunity could possibly be harnessed for B cell-targeting immunotherapy.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Linfócitos B
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Linfócitos do Interstício Tumoral
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Centro Germinativo
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Neoplasias
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article