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The extracellular matrix dictates regional competence for tumour initiation
Experiments in mice show that expression of the oncogene SmoM2 induces basal cell carcinoma in the ear epidermis but not in the back skin, and that this difference in susceptibility is regulated by the extracellular matrix.
- Nordin Bansaccal
- , Pauline Vieugue
- & Cédric Blanpain
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Article |
IL-1β+ macrophages fuel pathogenic inflammation in pancreatic cancer
Single-cell and spatial gene expression analyses of pancreatic ductal adenocarcinoma uncover a population of interleukin-1β-expressing macrophages that drive inflammatory reprogramming of neighboring tumour cells leading to disease progression and poor prognosis for patients.
- Nicoletta Caronni
- , Federica La Terza
- & Renato Ostuni
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Article |
CD300ld on neutrophils is required for tumour-driven immune suppression
A CRISPR–Cas9 screen in a tumour mouse model identifies CD300ld as a tumour receptor on polymorphonuclear myeloid-derived suppressor cells and in vivo experiments indicate that it is a promising target for cancer immunotherapy.
- Chaoxiong Wang
- , Xichen Zheng
- & Min Luo
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Article |
Metabolic programs of T cell tissue residency empower tumour immunity
A study describes the metabolic adaptations supporting differentiation, survival and function of tissue-resident memory CD8+ T cells and how to leverage them to enhance immunity against pathogens and tumours.
- Miguel Reina-Campos
- , Maximilian Heeg
- & Ananda W. Goldrath
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Article
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Non-cell-autonomous cancer progression from chromosomal instability
Chromosomal instability in cancer is linked to endoplasmic reticulum stress signalling, immune suppression and metastasis, which is mediated by the cGAS–STING pathway, suppression of which can reduce metastasis.
- Jun Li
- , Melissa J. Hubisz
- & Samuel F. Bakhoum
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Matters Arising |
Revisiting the intrinsic mycobiome in pancreatic cancer
- Ashley A. Fletcher
- , Matthew S. Kelly
- & Peter J. Allen
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Article |
Histone demethylase KDM5D upregulation drives sex differences in colon cancer
A murine colorectal cancer (CRC) model shows that mutant KRAS-STAT4-mediated upregulation of Y chromosome KDM5D contributes to the sex differences in KRAS-mutant CRC, providing an actionable therapeutic strategy for metastasis risk reduction for men afflicted with KRAS-mutant CRC.
- Jiexi Li
- , Zhengdao Lan
- & Ronald A. DePinho
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Review Article |
The neuroscience of cancer
This Review examines the interplay between the nervous system and tumours, from cancer initiation to progression and metastasis.
- Rebecca Mancusi
- & Michelle Monje
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Article
| Open Access
In situ tumour arrays reveal early environmental control of cancer immunity
Skin tumour array by microporation (STAMP) captures the dynamic relationships of spatial, cellular and molecular components of tumour rejection and has the potential to translate therapeutic concepts into successful clinical strategies.
- Guadalupe Ortiz-Muñoz
- , Markus Brown
- & Christine Moussion
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Article
| Open Access
Glioblastoma remodelling of human neural circuits decreases survival
High-grade gliomas functionally remodel neural circuits in the human brain, promoting tumour progression and impairing cognition.
- Saritha Krishna
- , Abrar Choudhury
- & Shawn L. Hervey-Jumper
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Article
| Open Access
The dietary sweetener sucralose is a negative modulator of T cell-mediated responses
Consumption of high doses of the sweetener sucralose has immunomodulatory effects in mice, as a result of reduced T cell proliferation and differentiation.
- Fabio Zani
- , Julianna Blagih
- & Karen H. Vousden
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Article
| Open Access
Single-cell spatial immune landscapes of primary and metastatic brain tumours
Imaging mass cytometry of human brain tumours provides spatial information that, combined with existing transcriptomic data, reveals the existence of a cellular neighbourhood containing a rare macrophage population associated with prolonged survival.
- Elham Karimi
- , Miranda W. Yu
- & Logan A. Walsh
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Article
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Single-cell spatial landscapes of the lung tumour immune microenvironment
Using imaging mass cytometry, the tumour and immunological spatial landscapes of 416 lung adenocarcinomas are characterized, which, when combined with deep learning, can predict clinical outcomes with high accuracy.
- Mark Sorin
- , Morteza Rezanejad
- & Logan A. Walsh
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Article |
Targeting TBK1 to overcome resistance to cancer immunotherapy
Targeting TBK1 is an effective strategy to overcome resistance to cancer immunotherapy.
- Yi Sun
- , Or-yam Revach
- & Russell W. Jenkins
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Article
| Open Access
Ovarian cancer mutational processes drive site-specific immune evasion
Multi-modal analysis of genomically unstable ovarian tumours characterizes the contribution of anatomical sites and mutational processes to evolutionary phenotypic divergence and immune resistance mechanisms.
- Ignacio Vázquez-García
- , Florian Uhlitz
- & Sohrab P. Shah
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Article
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Ras drives malignancy through stem cell crosstalk with the microenvironment
Aberrant crosstalk between cancer stem cells and their microenvironment triggers angiogenesis and TGFβ signalling, creating conditions that are conducive for hijacking leptin and leptin receptor signalling, which in turn launches downstream PI3K–AKT–mTOR signalling during the benign-to-malignant transition.
- Shaopeng Yuan
- , Katherine S. Stewart
- & Elaine Fuchs
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Article
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Effect of the intratumoral microbiota on spatial and cellular heterogeneity in cancer
Spatial profiling and single-cell RNA sequencing are used to map the spatial distribution of the microbiota within human tumours, revealing how intratumoral microbial communities contribute to tumour heterogeneity and cancer progression.
- Jorge Luis Galeano Niño
- , Hanrui Wu
- & Susan Bullman
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Article |
Liver tumour immune microenvironment subtypes and neutrophil heterogeneity
Tumour-associated neutrophil populations enriched in the myeloid-cell-enriched tumour immune microenvironment subtype are associated with unfavourable prognosis in humans and mice with liver cancer.
- Ruidong Xue
- , Qiming Zhang
- & Ning Zhang
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Article
| Open Access
Extracellular fluid viscosity enhances cell migration and cancer dissemination
Elevated viscosity counterintuitively increases the motility of various cell types in vitro and imprints mechanical memory to tumour cells, which enables them to disseminate more efficiently in vivo.
- Kaustav Bera
- , Alexander Kiepas
- & Konstantinos Konstantopoulos
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Article |
Opposing roles of hepatic stellate cell subpopulations in hepatocarcinogenesis
Subpopulations of cytokine-producing and myofibroblastic hepatic stellate cells, identified by single-cell RNA sequencing, protect against or promote the development of hepatocellular carcinoma via high expression of hepatocyte growth factor or type I collagen, respectively..
- Aveline Filliol
- , Yoshinobu Saito
- & Robert F. Schwabe
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Article
| Open Access
Collagenolysis-dependent DDR1 signalling dictates pancreatic cancer outcome
Cleaved and intact type I collagen have different effects on pancreatic ductal adenocarcinoma (PDAC), and remodelling of type I collagen—mediated through DDR1 signalling—is a prognostic indicator for the survival of patients with PDAC.
- Hua Su
- , Fei Yang
- & Michael Karin
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Article
| Open Access
LRRC15+ myofibroblasts dictate the stromal setpoint to suppress tumour immunity
LRRC15-positive cancer-associated fibroblasts constitute a pivotal axis in tumorigenesis and are potential therapeutic targets to improve responses to immune checkpoint blockade.
- Akshay T. Krishnamurty
- , Justin A. Shyer
- & Shannon J. Turley
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Review Article |
Inflammatory memory and tissue adaptation in sickness and in health
A Review on inflammatory memory in non-immune cells of different epithelia and neurons, and the potential mechanisms controlling these epigenetic memories and their implications in human health and disease.
- Shruti Naik
- & Elaine Fuchs
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Article |
Olfactory sensory experience regulates gliomagenesis via neuronal IGF1
A mouse model of gliomagenesis reveals that olfaction can directly regulate the genesis of gliomas, showing that sensory experience and gliomagenesis are linked and providing insight into the neural circuitry involved.
- Pengxiang Chen
- , Wei Wang
- & Chong Liu
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Article |
Tumour DDR1 promotes collagen fibre alignment to instigate immune exclusion
In mouse models of triple-negative breast cancer, the extracellular domain of the collagen receptor DDR1 has a role in tumour defence against the immune system, by aligning collagen fibres to obstruct immune infiltration.
- Xiujie Sun
- , Bogang Wu
- & Rong Li
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Article |
Tissue-resident macrophages provide a pro-tumorigenic niche to early NSCLC cells
Single-cell RNA sequencing and imaging of macrophages in human non-small cell lung cancer and in a mouse model of lung adenocarcinoma show that tissue-resident macrophages have a key role in early tumour progression.
- María Casanova-Acebes
- , Erica Dalla
- & Miriam Merad
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Article |
Hepatic stellate cells suppress NK cell-sustained breast cancer dormancy
Liver-resident natural killer (NK) cells sustain the dormancy of disseminated breast cancer cells, and a decrease in NK cells and increase in activated hepatic stellate cells is associated with the formation of liver metastases.
- Ana Luísa Correia
- , Joao C. Guimaraes
- & Mohamed Bentires-Alj
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Article |
Tracing oncogene-driven remodelling of the intestinal stem cell niche
By inducing changes in surrounding tissue, mutant intestinal stem cells create an unfavourable niche environment that gives them a competitive advantage over non-mutant neighbours.
- Min Kyu Yum
- , Seungmin Han
- & Benjamin D. Simons
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Article |
Cell-programmed nutrient partitioning in the tumour microenvironment
Positron emission tomography measurements of nutrient uptake in cells of the tumour microenvironment reveal cell-intrinsic partitioning in which glucose uptake is higher in myeloid cells, whereas glutamine is preferentially acquired by cancer cells.
- Bradley I. Reinfeld
- , Matthew Z. Madden
- & W. Kimryn Rathmell
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Article |
Creation of bladder assembloids mimicking tissue regeneration and cancer
Multilayer 3D reconstitution of bladder stem cells with stromal cells enables recapitulation of the architecture and molecular functions of bladder tissue.
- Eunjee Kim
- , Seoyoung Choi
- & Kunyoo Shin
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Article |
Inhibition of PCSK9 potentiates immune checkpoint therapy for cancer
Inhibiting the PCSK9 protein, a regulator of cholesterol metabolism, enhances immune checkpoint therapy in mouse models of cancer, in a manner that depends on the regulation of antigen-presenting MHC I molecules.
- Xinjian Liu
- , Xuhui Bao
- & Chuan-Yuan Li
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Article |
Tumoural activation of TLR3–SLIT2 axis in endothelium drives metastasis
Expression of the axon-guidance gene Slit2 in endothelium, induced by endothelial sensing of tumour-derived double-stranded RNA, promotes metastatic dissemination in mouse models of breast and lung cancer.
- Bernardo Tavora
- , Tobias Mederer
- & Sohail F. Tavazoie
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Article |
Mechanics of a multilayer epithelium instruct tumour architecture and function
Mathematical and experimental approaches are used to investigate the mechanical forces that shape the tumour architecture of two different common forms of skin cancer: basal cell carcinomas and invasive squamous cell carcinomas.
- Vincent F. Fiore
- , Matej Krajnc
- & Elaine Fuchs
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Article |
DNA of neutrophil extracellular traps promotes cancer metastasis via CCDC25
DNA from neutrophil extracellular traps interacts with the transmembrane receptor CCDC25 on cancer cells, activating the ILK-β-parvin pathway to enhance cell motility and promote distant metastases.
- Linbin Yang
- , Qiang Liu
- & Erwei Song
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Article |
Paracrine orchestration of intestinal tumorigenesis by a mesenchymal niche
Single-cell RNA-sequencing analysis of intestinal mesenchyme identified a population of fibroblasts that produce prostaglandin E2, which, when disrupted, prevented initiation of intestinal tumours.
- Manolis Roulis
- , Aimilios Kaklamanos
- & Richard A. Flavell
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Review Article |
Dietary modifications for enhanced cancer therapy
- Naama Kanarek
- , Boryana Petrova
- & David M. Sabatini
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Article |
Mutational signature in colorectal cancer caused by genotoxic pks+ E. coli
Organoids derived from human intestinal cells that are co-cultured with bacteria carrying the genotoxic pks+ island develop a distinct mutational signature associated with colorectal cancer.
- Cayetano Pleguezuelos-Manzano
- , Jens Puschhof
- & Hans Clevers
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Article |
Loss of p53 drives neuron reprogramming in head and neck cancer
MicroRNAs from head and neck cancer cells, shuttled to sensory neurons by extracellular vesicles, cause a shift to an adrenergic neuronal phenotype that promotes tumour progression.
- Moran Amit
- , Hideaki Takahashi
- & Jeffrey N. Myers
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Article |
An intra-tumoral niche maintains and differentiates stem-like CD8 T cells
The authors examine the immune cell infiltrates of human tumours and provide evidence for a population of CD8 T cells with stem-cell characteristics and proliferative capacity that reside in an antigen-presenting niche within tumours.
- Caroline S. Jansen
- , Nataliya Prokhnevska
- & Haydn Kissick
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Letter |
The fungal mycobiome promotes pancreatic oncogenesis via activation of MBL
In humans and mouse models, the mycobiome of pancreatic ductal adenocarcinoma tumours is markedly enriched in Malassezia species compared to that of normal pancreas, which implicates these pathogenic fungi in oncogenesis.
- Berk Aykut
- , Smruti Pushalkar
- & George Miller
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Article |
Electrical and synaptic integration of glioma into neural circuits
Neurons form synapses onto glioma cells, and depolarization of glioma membranes promotes glioma growth in vivo, whereas blocking electrochemical signalling blocks tumour growth.
- Humsa S. Venkatesh
- , Wade Morishita
- & Michelle Monje
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Article |
Glutamatergic synaptic input to glioma cells drives brain tumour progression
Neurons form glutamatergic synapses with glioma cells in mice and humans, and inhibition of AMPA receptors reduces glioma cell invasion and growth.
- Varun Venkataramani
- , Dimitar Ivanov Tanev
- & Thomas Kuner
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Article |
Metastatic-niche labelling reveals parenchymal cells with stem features
A cell-penetrating fluorescent marker is used to label cells in the metastatic tumour microenvironment, revealing a variety of cell types including parenchymal cells with lung stem-cell characteristics.
- Luigi Ombrato
- , Emma Nolan
- & Ilaria Malanchi
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Letter |
Loss of p53 triggers WNT-dependent systemic inflammation to drive breast cancer metastasis
Loss of p53 in mouse models of breast cancer leads to activation of WNT signalling, which promotes metastatic spread by inducing systemic neutrophilic inflammation.
- Max D. Wellenstein
- , Seth B. Coffelt
- & Karin E. de Visser
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Letter |
Flower isoforms promote competitive growth in cancer
A cell competition mechanism based on the differential expression of isoforms of Flower proteins is found in humans as well as Drosophila, and promotes tumorigenesis.
- Esha Madan
- , Christopher J. Pelham
- & Eduardo Moreno
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Letter |
Immune evasion before tumour invasion in early lung squamous carcinogenesis
The immune response is modulated at a early stage of carcinogenesis, such that both immune activation and evasion precede tumour invasion.
- Céline Mascaux
- , Mihaela Angelova
- & Jérôme Galon
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Article |
Progenitors from the central nervous system drive neurogenesis in cancer
In a mouse model of prostate cancer, neural progenitors from the central nervous system that express doublecortin infiltrate tumours and metastases, and can generate new adrenergic neurons in tumours.
- Philippe Mauffrey
- , Nicolas Tchitchek
- & Claire Magnon
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Letter |
Proteomics reveals NNMT as a master metabolic regulator of cancer-associated fibroblasts
The authors find that stromal methyltransferase nicotinamide N-methyltransferase (NNMT) regulates the transition of normal fibroblasts to cancer-associated fibroblasts through histone methylation and promotes ovarian cancer growth and metastasis.
- Mark A. Eckert
- , Fabian Coscia
- & Ernst Lengyel
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Letter |
Targeting LIF-mediated paracrine interaction for pancreatic cancer therapy and monitoring
A systematic proteomic investigation of disease mediators secreted by pancreatic stellate cells identifies leukaemia inhibitory factor (LIF) as a key factor that acts on cancer cells, promoting tumour progression and chemoresistance.
- Yu Shi
- , Weina Gao
- & Tony Hunter
PGE2 limits effector expansion of tumour-infiltrating stem-like CD8+ T cells