Faculty, Staff and Student Publications

Publication Date

10-7-2024

Journal

Nature Communications

DOI

10.1038/s41467-021-22872-z

PMID

34001881

PMCID

PMC8128874

PubMedCentral® Posted Date

5-17-2021

PubMedCentral® Full Text Version

Post-print

Abstract

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 due to 17q gain, BIRC5/survivin expression is upregulated in resistant MCL tumor cells and targeting BIRC5 results in marked tumor inhibition in preclinical models. In addition, we discover 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 reveals diverse and dynamic tumor and immune programs underlying therapy resistance in MCL.

Keywords

Cancer genomics, B-cell lymphoma

Comments

This article has been corrected. See Nat Commun. 2024 Oct 7;15:8668.

Published Open-Access

yes

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41467_2024_Article_52013.pdf (449 kB)
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