Abstract：
:Cancer-induced immune responses affect tumour progression and therapeutic response. In multiple murine models and clinical datasets, we identified large variations of neutrophils and macrophages that define 'immune subtypes' of triple-negative breast cancer (TNBC), including neutrophil-enriched (NES) and macrophage-enriched subtypes (MES). Different tumour-intrinsic pathways and mutual regulation between macrophages (or monocytes) and neutrophils contribute to the development of a dichotomous myeloid compartment. MES contains predominantly macrophages that are CCR2-dependent and exhibit variable responses to immune checkpoint blockade (ICB). NES exhibits systemic and local accumulation of immunosuppressive neutrophils (or granulocytic myeloid-derived suppressor cells), is resistant to ICB, and contains a minority of macrophages that seem to be unaffected by CCR2 knockout. A MES-to-NES conversion mediated acquired ICB resistance of initially sensitive MES models. Our results demonstrate diverse myeloid cell frequencies, functionality and potential roles in immunotherapies, and highlight the need to better understand the inter-patient heterogeneity of the myeloid compartment.
journal_name
Nat Cell Bioljournal_title
Nature cell biologyauthors
Kim IS,Gao Y,Welte T,Wang H,Liu J,Janghorban M,Sheng K,Niu Y,Goldstein A,Zhao N,Bado I,Lo HC,Toneff MJ,Nguyen T,Bu W,Jiang W,Arnold J,Gu F,He J,Jebakumar D,Walker K,Li Y,Mo Q,Westbrook TF,Zong C,Rao A,doi
10.1038/s41556-019-0373-7subject
Has Abstractpub_date
2019-09-01 00:00:00pages
1113-1126issue
9eissn
1465-7392issn
1476-4679pii
10.1038/s41556-019-0373-7journal_volume
21pub_type
杂志文章abstract：:Clathrin-coated vesicles mediate endocytosis and transport between the trans-Golgi network (TGN) and endosomes in eukaryotic cells. Clathrin adaptors play central roles in coat assembly, interacting with clathrin, cargo and membranes. Two main types of clathrin adaptor act in TGN-endosome traffic: GGA proteins and the...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb2427
更新日期：2012-02-19 00:00:00
abstract：:Dyneins are large microtubule motor proteins required for mitosis, intracellular transport and ciliary and flagellar motility. They generate force through a power-stroke mechanism, which is an ATP-consuming cycle of pre- and post-power-stroke conformational changes that cause relative motion between different dynein d...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb2939
更新日期：2014-05-01 00:00:00
abstract：:Chromosome loss or gain is associated with a large number of solid cancers, providing genomic plasticity and thus adaptability to cancer cells. Numerical centrosome abnormalities arising from centrosome over-duplication or failed cytokinesis are a recognized cause of aneuploidy. In higher eukaryotic cells, the centros...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb1735
更新日期：2008-06-01 00:00:00
abstract：:Rad23 is a nucleotide-excision repair protein with a previously unknown biochemical function. We determined that yeast and human Rad23 inhibited multi-ubiquitin (Ub) chain formation and the degradation of proteolytic substrates. Significantly, Rad23 could be co-precipitated with a substrate that contained a short mult...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/35023547
更新日期：2000-09-01 00:00:00
abstract：:In the version of this Article originally published, ref. 52 was incorrectly only attributed to its corresponding author, Fre, S., and an older title was used. The correct citation should have been: Lilja, A. M. et al. Clonal analysis of Notch1-expressing cells reveals the existence of unipotent stem cells that retain...
journal_title：Nature cell biology
pub_type： 已发布勘误
doi：10.1038/s41556-018-0164-6
更新日期：2018-09-01 00:00:00
abstract：:The seminal observation that mechanical signals can elicit changes in biochemical signalling within cells, a process commonly termed mechanosensation and mechanotransduction, has revolutionized our understanding of the role of cell mechanics in various fundamental biological processes, such as cell motility, adhesion,...
journal_title：Nature cell biology
pub_type： 杂志文章,评审
doi：10.1038/ncb3524
更新日期：2017-05-31 00:00:00
abstract：:To control cell proliferation, signal transduction needs to regulate the cell-cycle machinery. Recent findings show that Akt - a major kinase that coordinates diverse signalling pathways - phosphorylates Skp2, a subunit of the SCF-Skp2 ubiquitin ligase that targets key cell-cycle regulators. Akt1-dependent phosphoryla...
journal_title：Nature cell biology
pub_type： 评论,新闻
doi：10.1038/ncb0409-377
更新日期：2009-04-01 00:00:00
abstract：:The directional movement of cells in a gradient of external stimulus is termed chemotaxis and is important in many aspects of development and differentiated cell function. Phophoinositide 3-kinases (PI(3)Ks) are thought to have critical roles within the gradient-sensing machinery of a variety of highly motile cells, s...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb1517
更新日期：2007-01-01 00:00:00
abstract：:Cells of multicellular organisms need to adopt specific morphologies. However, the molecular mechanisms bringing about membrane topology changes are far from understood-mainly because knowledge of membrane-shaping proteins that can promote local membrane curvatures is still limited. Our analyses unveiled that several ...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/s41556-019-0381-7
更新日期：2019-10-01 00:00:00
abstract：:Research on genome stability and integrity now extends far beyond the biochemistry of DNA repair to encompass signal transduction pathways that span numerous aspects of cellular life. Derailed genomic integrity pathways can result in debilitating genetic disorders, premature ageing, predisposition to cancer and degene...
journal_title：Nature cell biology
pub_type：
doi：10.1038/ncb1004-923
更新日期：2004-10-01 00:00:00
abstract：:To generate the various tissues and organs that build up the adult body, plants and animals require organized formative cell divisions and correct cell specification. In plants, these processes are controlled mainly by phytohormones and transcriptional networks. Recently, ligand-receptor-like kinase signalling pathway...
journal_title：Nature cell biology
pub_type： 杂志文章,评审
doi：10.1038/ncb1009-1166
更新日期：2009-10-01 00:00:00
abstract：:The asymmetric segregation of cell-fate determinants and the generation of daughter cells of different sizes rely on the correct orientation and position of the mitotic spindle. In the Drosophila embryo, the determinant Prospero is localized basally and is segregated equally to daughters of similar cell size during ep...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/71323
更新日期：2000-01-01 00:00:00
abstract：:The function and regulation of repetitive DNA, the 'dark matter' of the genome, is still only rudimentarily understood. Now a study investigating DNA replication of repetitive centromeric chromosome segments has started to expose a fascinating replication program that involves suppression of ATR signalling, in particu...
journal_title：Nature cell biology
pub_type： 评论,杂志文章
doi：10.1038/ncb3367
更新日期：2016-05-27 00:00:00
abstract：:Telomere attrition and other forms of telomere damage can activate the ATM kinase pathway. What generates the DNA damage signal at mammalian chromosome ends or at other double-strand breaks is not known. Telomere dysfunction is often accompanied by disappearance of the 3' telomeric overhang, raising the possibility th...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb1275
更新日期：2005-07-01 00:00:00
abstract：:Dozens of proteins capture, polymerize and reshape the clathrin lattice during clathrin-mediated endocytosis (CME). How or if this ensemble of proteins is organized in relation to the clathrin coat is unknown. Here, we map key molecules involved in CME at the nanoscale using correlative super-resolution light and tran...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb3498
更新日期：2017-04-01 00:00:00
abstract：:The Drosophila fruitless (fru) gene product Fru has been postulated to be a neural sex-determination factor that directs the development of at least two male-specific characteristics, namely courtship behaviour and formation of the muscle of Lawrence (MOL). The fru gene encodes a putative transcription factor with a B...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/35019537
更新日期：2000-08-01 00:00:00
abstract：:Science denial is not new but, in the digital age, evidence-based conclusions appear to be increasingly threatened by beliefs based on emotion and isolated personal experience. When confronting a post-truth world, scientists must defend the scientific method and increase public engagement. ...
journal_title：Nature cell biology
pub_type： 社论
doi：10.1038/s41556-018-0231-z
更新日期：2018-11-01 00:00:00
abstract：:Lamellipodia/ruffles and filopodia are protruding organelles containing short and highly branched or long and unbranched actin filaments, respectively. The microscopic morphology, dynamic development and protein signature of both lamellipodia/ruffles and filopodia have been investigated; however, little is known about...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb1745
更新日期：2008-07-01 00:00:00
abstract：:YAP (Yes-associated protein) is a transcription co-activator in the Hippo tumour suppressor pathway and controls cell growth, tissue homeostasis and organ size. YAP is inhibited by the kinase Lats, which phosphorylates YAP to induce its cytoplasmic localization and proteasomal degradation. YAP induces gene expression ...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb3111
更新日期：2015-04-01 00:00:00
abstract：:The accurate spatial and temporal coordination of cell polarization with DNA replication and segregation guarantees the fidelity of genetic transmission. Here we report that in Saccharomyces cerevisiae, a build-up or burst of G1 cyclin-dependent kinase (CDK) activity through activation of the cyclin genes CLN1,2 and P...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb1078
更新日期：2004-01-01 00:00:00
abstract：:Most invasive solid tumours display predominantly collective invasion, in which groups of cells invade the peritumoral stroma while maintaining cell-cell contacts. As the concepts and experimental models for functional analysis of collective cancer cell invasion are rapidly developing, we propose a framework for addre...
journal_title：Nature cell biology
pub_type： 杂志文章,评审
doi：10.1038/ncb2548
更新日期：2012-08-01 00:00:00
abstract：:In the version of this Resource originally published, owing to a technical error an incorrect file was used for Supplementary Table 2; this has now been replaced with the correct file. ...
journal_title：Nature cell biology
pub_type： 已发布勘误
doi：10.1038/s41556-018-0166-4
更新日期：2018-10-01 00:00:00
abstract：:Direct reprogramming by forced expression of transcription factors can convert one cell type into another. Thus, desired cell types can be generated bypassing pluripotency. However, direct reprogramming towards renal cells remains an unmet challenge. Here, we identify renal cell fate-inducing factors on the basis of t...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb3437
更新日期：2016-12-01 00:00:00
abstract：:When co-translationally inserted into endoplasmic reticulum (ER) membranes, newly synthesized proteins encounter the lumenal environment of the ER, which contains chaperone proteins that facilitate the folding reactions necessary for protein oligomerization, maturation and export from the ER. Here we show, using a tem...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/35010558
更新日期：2000-05-01 00:00:00
abstract：:Examination of the tumour suppressor adenomatous polyposis coli (APC) has shown that it may be multifunctional. Recent work has demonstrated dynamic interactions of APC with the microtubule cytoskeleton, supporting the idea that APC has an important function in cell migration. ...
journal_title：Nature cell biology
pub_type： 新闻,评审
doi：10.1038/35008685
更新日期：2000-04-01 00:00:00
abstract：:Tau is an abundant microtubule-associated protein in neurons. Tau aggregation into insoluble fibrils is a hallmark of Alzheimer's disease and other types of dementia1, yet the physiological state of tau molecules within cells remains unclear. Using single-molecule imaging, we directly observe that the microtubule latt...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/s41556-019-0375-5
更新日期：2019-09-01 00:00:00
abstract：:The remarkable stability of gene expression in somatic cells is exemplified by the way memory of an active gene state is retained when an endoderm cell nucleus is transplanted to an enucleated egg. Here we analyse the mechanism of a similar example of epigenetic memory. We find that memory can persist through 24 cell ...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb1674
更新日期：2008-01-01 00:00:00
abstract：:Cancer-associated fibroblasts (CAFs) promote tumour invasion and metastasis. We show that CAFs exert a physical force on cancer cells that enables their collective invasion. Force transmission is mediated by a heterophilic adhesion involving N-cadherin at the CAF membrane and E-cadherin at the cancer cell membrane. Th...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb3478
更新日期：2017-03-01 00:00:00
abstract：:The formation of axon trajectories requires integration of local adhesive interactions with directional information from attractive and repulsive cues. Here, we show that these two types of information are functionally integrated; activation of the transmembrane receptor Roundabout (Robo) by its ligand, the secreted r...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/ncb858
更新日期：2002-10-01 00:00:00
abstract：:The resolution of joint molecules that link recombining sister chromatids is essential for chromosome segregation. Here, we determine the fate of unresolved recombination intermediates arising in cells lacking two nucleases required for resolution (GEN1 -/- knockout cells depleted of MUS81). We find that intermediates...
journal_title：Nature cell biology
pub_type： 杂志文章
doi：10.1038/s41556-017-0011-1
更新日期：2018-01-01 00:00:00
