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| Open AccessT cell receptor β-chain-targeting chimeric antigen receptor T cells against T cell malignancies
Healthy T cells are polyclonal, while malignant T cells are developing via clonal expansion. Here authors show that T cell tumours could be eradicated by chimeric antigen receptor T cells targeting the T cell receptor (TCR) β-chain that is specific to malignant T cells, while healthy T cells using diverse TCR β-chains are spared.
- Fanlin Li
- , Huihui Zhang
- & Xuanming Yang
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| Open AccessIRF4 drives clonal evolution and lineage choice in a zebrafish model of T-cell lymphoma
IRF4 is a regulator of immune function, and is overexpressed in lymphoid neoplasms. Here, the authors utilise single cell RNA-seq to show the abundance of double-negative T cells in IRF4 driven zebrafish tumour models, and identify sensitivity of these tumours to BRD inhibition.
- Stella Amanda
- , Tze King Tan
- & Takaomi Sanda
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Article
| Open AccessSingle-cell transcriptomics links malignant T cells to the tumor immune landscape in cutaneous T cell lymphoma
Cutaneous T cell lymphomas (CTCL) are still poorly characterised at the molecular and single-cell level. Here, the authors analyse CTCL patient samples using single-cell RNA-seq, TCR and whole-exome sequencing, revealing the molecular profiles of malignant T cells and their association with the microenvironment and clinical outcomes.
- Xiangjun Liu
- , Shanzhao Jin
- & Yang Wang
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| Open AccessImmune cell topography predicts response to PD-1 blockade in cutaneous T cell lymphoma
PD-1 blockade is effective for only a subset of patients with cutaneous T cell lymphomas. Here, the authors report a spatial biomarker that uses immune and cancer cell topography to predict response to PD-1 blockade in this disease.
- Darci Phillips
- , Magdalena Matusiak
- & Garry P. Nolan
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| Open AccessSuper-enhancer-based identification of a BATF3/IL-2R−module reveals vulnerabilities in anaplastic large cell lymphoma
Anaplastic large cell lymphoma (ALCL) is an aggressive T-cell lymphoma often with poor prognosis. To identify genes defining ALCL cell state and dependencies, the authors here characterize ALCL-specific super-enhancers and describe the BATF3/IL-2R−module as a therapeutic opportunity for ALCL.
- Huan-Chang Liang
- , Mariantonia Costanza
- & Olaf Merkel
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| Open AccessChronological genome and single-cell transcriptome integration characterizes the evolutionary process of adult T cell leukemia-lymphoma
Characterising the clonal architecture of Adult T-cell leukemia-lymphoma (ATL) remains crucial. Here, the authors develop a capture-based sequencing panel and use deep DNA and single cell RNA sequencing and report distinct genomic and transcriptomic features associated with subclonal evolution.
- Makoto Yamagishi
- , Miyuki Kubokawa
- & Kaoru Uchimaru
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| Open AccessFusion transcripts FYN-TRAF3IP2 and KHDRBS1-LCK hijack T cell receptor signaling in peripheral T-cell lymphoma, not otherwise specified
Peripheral T cell lymphoma (PTCL) not otherwise specified (NOS) is a subgroup of PTCL, which has no distinctive features and is poorly characterized at the genetic level. Here, the authors identify two fusion transcripts that activate T cell receptor complex signalling and confer therapeutic vulnerability in PTCL-NOS.
- Koen Debackere
- , Lukas Marcelis
- & Daan Dierickx
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Article
| Open AccessTHZ1 targeting CDK7 suppresses STAT transcriptional activity and sensitizes T-cell lymphomas to BCL2 inhibitors
T-cell lymphomas are aggressive diseases associated with poor outcome. Here, the authors show that the THZ1, a CDK7 inhibitor, suppresses STAT transcriptional activity leading to apoptosis and sensitization to BCL2 inhibitors in T-cell lymphomas.
- Florencia Cayrol
- , Pannee Praditsuktavorn
- & Leandro Cerchietti
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Article
| Open AccessType II enteropathy-associated T-cell lymphoma features a unique genomic profile with highly recurrent SETD2 alterations
Enteropathy associated T-cell lymphoma -EATL- affects the intestine and there are two different subtypes. In this study, the authors carry out exome sequencing of the type II variant and find that it is characterized by recurrent mutations in the histone methyltransferase SETD2 that are accompanied by altered H3K6 methylation.
- Annalisa Roberti
- , Maria Pamela Dobay
- & Laurence de Leval
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Article
| Open AccessGenomic analyses reveal recurrent mutations in epigenetic modifiers and the JAK–STAT pathway in Sézary syndrome
Sézary syndrome is a T cell malignancy that has been poorly characterized at the genome level. In this study, Kielet al. perform whole-genome analyses and identify mutations in the JAK–STAT pathway and show that primary cells are sensitive to JAK inhibitors.
- Mark J. Kiel
- , Anagh A. Sahasrabuddhe
- & Kojo S. J. Elenitoba-Johnson
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Article
| Open AccessHigh-resolution analysis of the human T-cell receptor repertoire
Immune system diversity is generated by V(D)J recombination, leading to clonal T-cell lineages. Here the authors investigate the events leading to T-cell diversity through the use of a modified PCR technique combined with deep sequencing.
- Eliana Ruggiero
- , Jan P. Nicolay
- & Christof von Kalle
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Article
| Open AccessSite- and allele-specific polycomb dysregulation in T-cell leukaemia
TAL1 is frequently deregulated in T-cell acute lymphoblastic leukaemias, but the mechanism remains largely unclear. Here the authors show that microinsertions upstream of TAL1 cause its epigenetic reactivation, and that the mode of TAL1activation correlates with prognosis.
- Jean-Marc Navarro
- , Aurore Touzart
- & Bertrand Nadel
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Activating mutations of STAT5B and STAT3 in lymphomas derived from γδ-T or NK cells
NK-cell and γδ-T cell lymphoma share clinic-pathological features; however the driving mutations are largely unknown. Here the authors, using a combination of RNA-Seq analysis, targeted re-sequencing and functional analysis, identify frequent activating mutations in STAT3 and STAT5Bthat may be driver mutations in these diseases.
- Can Küçük
- , Bei Jiang
- & Wing C. Chan
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Loss of NDRG2 expression activates PI3K-AKT signalling via PTEN phosphorylation in ATLL and other cancers
The PI3K pathway that encompasses the tumour suppressor PTEN contributes to tumourigenesis in adult T-cell leukaemia-lymphoma (ATLL). In this study, Nakahata et al. show that PTEN is dephosphorylated by NDRG2, and that loss of NDGR2 in ATLL results in the activation of the PI3K pathway.
- Shingo Nakahata
- , Tomonaga Ichikawa
- & Kazuhiro Morishita