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Longitudinal Single-Cell Profiling Reveals Molecular Heterogeneity and Tumor-Immune Evolution in Refractory Mantle Cell Lymphoma

The mechanisms driving therapeutic resistance and poor outcomes of mantle cell lymphoma (MCL) are incompletely understood. We characterize the cellular and molecular heterogeneity within and across patients and delineate the dynamic evolution of tumor and immune cell compartments at single cell resolution in longitudinal specimens from ibrutinib-sensitive patients and non-responders. Temporal activation of multiple cancer hallmark pathways and acquisition of 17q are observed in a refractory MCL. Multi-platform validation is performed at genomic and cellular levels in PDX models and larger patient cohorts. We demonstrate that the molecular targeting of BIRC5/survivin, locates at 17q and upregulates in resistant MCL tumor cells, results in marked tumor inhibition in preclinical models. In addition, we discovere notable differences in the tumor microenvironment including progressive dampening of CD8+ T cells and aberrant cell-to-cell communication networks in refractory MCLs. This study reveales diverse and dynamic tumor and immune programs underlying therapy resistance in MCL.

Click on a Dataset ID in the table below to learn more, and to find out who to contact about access to these data

Dataset ID Description Technology Samples
EGAD00001006994 Illumina HiSeq 4000 31
Publications Citations
Longitudinal single-cell profiling reveals molecular heterogeneity and tumor-immune evolution in refractory mantle cell lymphoma.
Nat Commun 12: 2021 2877
Advances in single-cell RNA sequencing and its applications in cancer research.
J Hematol Oncol 16: 2023 98
The HSP90-MYC-CDK9 network drives therapeutic resistance in mantle cell lymphoma.
Exp Hematol Oncol 13: 2024 14