Integrated single cell analysis reveals co-evolution of malignant B cells and tumor micro-environment in transformed follicular lymphoma.
Cancer Cell
; 42(6): 1003-1017.e6, 2024 Jun 10.
Article
em En
| MEDLINE
| ID: mdl-38861923
ABSTRACT
Histological transformation of follicular lymphoma (FL) to aggressive forms is associated with poor outcome. Phenotypic consequences of this evolution and its impact on the tumor microenvironment (TME) remain unknown. We perform single-cell whole genome sequencing (scWGS) and transcriptome sequencing (scWTS) of 11 paired pre/post-transformation patient samples and scWTS of additional samples from patients without transformation. Our analysis reveals evolutionary dynamics of transformation at single-cell resolution, highlighting a shifting TME landscape, with an emerging immune-cell exhaustion signature, co-evolving with the shifting malignant B phenotype in a regulatory ecosystem. Integration of scWGS and scWTS identifies malignant cell pathways upregulated during clonal tumor evolution. Using multi-color immunofluorescence, we transfer these findings to a TME-based transformation biomarker, subsequently validated in two independent pretreatment cohorts. Taken together, our results provide a comprehensive view of the combined genomic and phenotypic evolution of malignant cells during transformation and shifting crosstalk between malignant cells and the TME.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Linfoma Folicular
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Análise de Célula Única
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Microambiente Tumoral
Limite:
Humans
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article