Extrinsic and intrinsic drivers of natural killer cell clonality DOI Creative Commons
Timo Rückert, Chiara Romagnani

Immunological Reviews, Год журнала: 2024, Номер 323(1), С. 80 - 106

Опубликована: Март 20, 2024

Summary Clonal expansion of antigen‐specific lymphocytes is the fundamental mechanism enabling potent adaptive immune responses and generation memory. Accompanied by pronounced epigenetic remodeling, massive proliferation individual cells generates a critical mass effectors for control acute infections, as well pool memory protecting against future pathogen encounters. Classically associated with system, recent work has demonstrated that innate to human cytomegalovirus (CMV) infection stably maintained large clonal expansions natural killer (NK) cells, raising questions on mechanisms selection in absence re‐arranged antigen receptors. Here, we discuss NK cell context underlying competition propose alternative might decide success their counterparts. We integration external cues cell‐intrinsic sources heterogeneity, such variegated receptor expression, transcriptional states, somatic variants, compose bottleneck selection, contributing size clones.

Язык: Английский

Natural killer cell therapies DOI
Éric Vivier, Lucas Rebuffet, Émilie Narni-Mancinelli

и другие.

Nature, Год журнала: 2024, Номер 626(8000), С. 727 - 736

Опубликована: Фев. 21, 2024

Язык: Английский

Процитировано

140
Ineffective control of Epstein-Barr-virus-induced autoimmunity increases the risk for multiple sclerosis DOI Creative Commons
Hannes Vietzen, S. Berger, Laura M. Kühner

и другие.

Cell, Год журнала: 2023, Номер 186(26), С. 5705 - 5718.e13

Опубликована: Дек. 1, 2023

Multiple sclerosis (MS) is a demyelinating disease of the CNS. Epstein-Barr virus (EBV) contributes to MS pathogenesis because high levels EBV EBNA386–405-specific antibodies cross react with CNS-derived GlialCAM370–389. However, it unclear why only some individuals such autoreactive antibody titers develop MS. Here, we show that cells are eliminated by distinct immune responses, which determined genetic variations host, as well infecting and human cytomegalovirus (HCMV). We demonstrate potent cytotoxic NKG2C+ NKG2D+ natural killer (NK) EBV-specific T cell responses kill GlialCAM370–389-specific cells. Furthermore, evasion these was induced EBV-variant-specific upregulation immunomodulatory HLA-E. These defined host pre-dispositions associated an up 260-fold increased risk Our findings thus allow early identification patients at for suggest additional therapeutic options against

Язык: Английский

Процитировано

78
High-dimensional single-cell analysis of human natural killer cell heterogeneity DOI Creative Commons
Lucas Rebuffet, Janine Melsen,

Bertrand Escalière

и другие.

Nature Immunology, Год журнала: 2024, Номер 25(8), С. 1474 - 1488

Опубликована: Июль 2, 2024

Abstract Natural killer (NK) cells are innate lymphoid (ILCs) contributing to immune responses microbes and tumors. Historically, their classification hinged on a limited array of surface protein markers. Here, we used single-cell RNA sequencing (scRNA-seq) cellular indexing transcriptomes epitopes by (CITE-seq) dissect the heterogeneity NK cells. We identified three prominent cell subsets in healthy human blood: NK1, NK2 NK3, further differentiated into six distinct subgroups. Our findings delineate molecular characteristics, key transcription factors, biological functions, metabolic traits cytokine each subgroup. These data also suggest two separate ontogenetic origins for cells, leading divergent transcriptional trajectories. Furthermore, analyzed distribution lung, tonsils intraepithelial lymphocytes isolated from individuals 22 tumor types. This standardized terminology aims at fostering clarity consistency future research, thereby improving cross-study comparisons.

Язык: Английский

Процитировано

53
Pan-cancer profiling of tumor-infiltrating natural killer cells through transcriptional reference mapping DOI Creative Commons
Herman Netskar, Aline Pfefferle,

Jodie P. Goodridge

и другие.

Nature Immunology, Год журнала: 2024, Номер 25(8), С. 1445 - 1459

Опубликована: Июль 2, 2024

The functional diversity of natural killer (NK) cell repertoires stems from differentiation, homeostatic, receptor-ligand interactions and adaptive-like responses to viral infections. In the present study, we generated a single-cell transcriptional reference map healthy human blood- tissue-derived NK cells, with temporal resolution fate-specific expression gene-regulatory networks defining differentiation. Transfer learning facilitated incorporation tumor-infiltrating transcriptomes (39 datasets, 7 solid tumors, 427 patients) into analyze tumor microenvironment (TME)-induced perturbations. Of six functionally distinct states identified, dysfunctional stressed CD56

Язык: Английский

Процитировано

20
Interleukin-21 engineering enhances NK cell activity against glioblastoma via CEBPD DOI Creative Commons
Mayra Shanley, May Daher, Jinzhuang Dou

и другие.

Cancer Cell, Год журнала: 2024, Номер 42(8), С. 1450 - 1466.e11

Опубликована: Авг. 1, 2024

Glioblastoma (GBM) is an aggressive brain cancer with limited therapeutic options. Natural killer (NK) cells are innate immune strong anti-tumor activity and may offer a promising treatment strategy for GBM. We compared the anti-GBM of NK engineered to express interleukin (IL)-15 or IL-21. Using multiple in vivo models, IL-21 were superior IL-15 both terms safety long-term activity, locoregionally administered proving toxic ineffective at tumor control. displayed unique chromatin accessibility signature, CCAAT/enhancer-binding proteins (C/EBP), especially CEBPD, serving as key transcription factors regulating their enhanced function. Deletion CEBPD resulted loss cell potency while its overexpression increased cytotoxicity metabolic fitness. These results suggest that IL-21, through C/EBP factors, drives epigenetic reprogramming cells, enhancing efficacy against

Язык: Английский

Процитировано

18
Mitochondrial genetics through the lens of single-cell multi-omics DOI
Lena Nitsch,

Caleb A Lareau,

Leif S Ludwig

и другие.

Nature Genetics, Год журнала: 2024, Номер 56(7), С. 1355 - 1365

Опубликована: Июль 1, 2024

Язык: Английский

Процитировано

17
Circulating NK cells establish tissue residency upon acute infection of skin and mediate accelerated effector responses to secondary infection DOI Creative Commons

Tommaso Torcellan,

Christin Friedrich,

Rémi Doucet-Ladevèze

и другие.

Immunity, Год журнала: 2023, Номер 57(1), С. 124 - 140.e7

Опубликована: Дек. 28, 2023

Natural killer (NK) cells are present in the circulation and can also be found residing tissues, these populations exhibit distinct developmental requirements thought to differ terms of ontogeny. Here, we investigate whether circulating conventional NK (cNK) develop into long-lived tissue-resident (trNK) following acute infections. We that viral bacterial infections skin triggered recruitment cNK their differentiation Tcf1

Язык: Английский

Процитировано

29
Natural Killer Cell-Based Immunotherapy against Glioblastoma DOI Open Access
Takayuki Morimoto, Tsutomu Nakazawa, Ryosuke Maeoka

и другие.

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(3), С. 2111 - 2111

Опубликована: Янв. 20, 2023

Glioblastoma (GBM) is the most aggressive and malignant primary brain tumor in adults. Despite multimodality treatment involving surgical resection, radiation therapy, chemotherapy, tumor-treating fields, median overall survival (OS) after diagnosis approximately 2 years 5-year OS poor. Considering poor prognosis, novel strategies are needed, such as immunotherapies, which include chimeric antigen receptor T-cell immune checkpoint inhibitors, vaccine oncolytic virus therapy. However, these therapies have not achieved satisfactory outcomes. One reason for this that mainly based on activating T cells controlling GBM progression. Natural killer (NK) cell-based immunotherapy involves new feature of recognizing via differing mechanisms from immunotherapy. In review, we focused NK a strategy.

Язык: Английский

Процитировано

24
Memory B cell subsets have divergent developmental origins that are coupled to distinct imprinted epigenetic states DOI

Derrick Callahan,

Shuchi Smita, Stephen Joachim

и другие.

Nature Immunology, Год журнала: 2024, Номер 25(3), С. 562 - 575

Опубликована: Янв. 10, 2024

Язык: Английский

Процитировано

14
Convergent epigenetic evolution drives relapse in acute myeloid leukemia DOI Creative Commons
Kevin A. Nuno, Armon Azizi,

Thomas Koehnke

и другие.

eLife, Год журнала: 2024, Номер 13

Опубликована: Апрель 22, 2024

Relapse of acute myeloid leukemia (AML) is highly aggressive and often treatment refractory. We analyzed previously published AML relapse cohorts found that 40% relapses occur without changes in driver mutations, suggesting non-genetic mechanisms drive a large proportion cases. therefore characterized epigenetic patterns using 26 matched diagnosis-relapse samples with ATAC-seq. This analysis identified relapse-specific chromatin accessibility signature for mutationally stable AML, undergoes evolution at independent mutational changes. Analysis stem cell (LSC) indicated this leukemic compartment underwent significantly less than non-LSCs, while non-LSCs reflected overall the bulk leukemia. Finally, we used single-cell ATAC-seq paired mitochondrial sequencing (mtscATAC) to map clones from diagnosis into along their features. distinct mitochondrially-defined exhibit more similar relative diagnosis, demonstrating convergent relapsed AML. These results demonstrate feature can following induction chemotherapy.

Язык: Английский

Процитировано

13