Featured
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Using DNA sequencing data to quantify T cell fraction and therapy response
A robust, cost-effective technique based on whole-exome sequencing data can be used to characterize immune infiltrates, relate the extent of these infiltrates to somatic changes in tumours, and enables prediction of tumour responses to immune checkpoint inhibition therapy.
- Robert Bentham
- , Kevin Litchfield
- & Nicholas McGranahan
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Functional HPV-specific PD-1+ stem-like CD8 T cells in head and neck cancer
An analysis of human papillomavirus (HPV)-specific CD8 T cells in patients with head and neck cancer identifies functional PD-1+TCF-1+CD8 T cells in the tumour with implications for therapeutic vaccination and PD-1 directed immunotherapy.
- Christiane S. Eberhardt
- , Haydn T. Kissick
- & Rafi Ahmed
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Phenotype, specificity and avidity of antitumour CD8+ T cells in melanoma
The authors use single-cell profiling and T cell receptor specificity screening to show how tumour antigen recognition shapes the phenotypes of CD8+ T cells and antitumour immune responses.
- Giacomo Oliveira
- , Kari Stromhaug
- & Catherine J. Wu
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Article
| Open AccessTranscriptional programs of neoantigen-specific TIL in anti-PD-1-treated lung cancers
Single-cell RNA sequencing and T cell receptor sequencing are combined to identify transcriptional programs specific to mutation-associated neoantigen-specific T cells in non-small cell lung cancers treated with anti-PD-1, providing insights into resistance to PD-1 blockade.
- Justina X. Caushi
- , Jiajia Zhang
- & Kellie N. Smith
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TIM-3 restrains anti-tumour immunity by regulating inflammasome activation
Mouse genetic studies and single-cell transcriptome analysis demonstrate that TIM-3 on dendritic cells has a key role in regulating antitumour immunity via inflammasome activation and is a potential target for anticancer therapy.
- Karen O. Dixon
- , Marcin Tabaka
- & Vijay K. Kuchroo
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Epigenetic silencing by SETDB1 suppresses tumour intrinsic immunogenicity
A CRISPR–Cas9 screen of chromatin regulators in mouse tumour models treated with immune checkpoint blockade identifies SETDB1 as an epigenetic checkpoint protein that suppresses tumour-intrinsic immunogenicity.
- Gabriel K. Griffin
- , Jingyi Wu
- & Bradley E. Bernstein
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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
| Open AccessA vaccine targeting mutant IDH1 in newly diagnosed glioma
A phase 1 clinical trial provides evidence that a vaccine against mutant IDH1 is safe and produces a T helper immune response in patients with glioma.
- Michael Platten
- , Lukas Bunse
- & Wolfgang Wick
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Lipid signalling enforces functional specialization of Treg cells in tumours
Identification of a metabolic checkpoint involving lipid signalling that is specific to regulatory T cells (Treg cells) in the tumour microenvironment raises the possibility of targeting this checkpoint for treatment of cancer.
- Seon Ah Lim
- , Jun Wei
- & Hongbo Chi
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Metabolic support of tumour-infiltrating regulatory T cells by lactic acid
The tumour microenvironment is low in glucose and high in the alternative metabolite lactate, which regulatory T cells are shown here to use, maintaining their ability to suppress effector immune cells.
- McLane J. Watson
- , Paolo D. A. Vignali
- & Greg M. Delgoffe
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CTLA-4 blockade drives loss of Treg stability in glycolysis-low tumours
CTLA-4 promotes glucose uptake by tumour-infiltrating regulatory T cells, making them unstable.
- Roberta Zappasodi
- , Inna Serganova
- & Taha Merghoub
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Article
| Open AccessIgA transcytosis and antigen recognition govern ovarian cancer immunity
In patients with high-grade serous ovarian cancer, robust and protective humoral responses are dominated by B-cell-derived polyclonal IgA that binds to polymeric IgA receptors that are universally expressed on ovarian cancer cells.
- Subir Biswas
- , Gunjan Mandal
- & Jose R. Conejo-Garcia
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Mechanism of EBV inducing anti-tumour immunity and its therapeutic use
Expression of the Epstein–Barr virus protein LMP1 in B cells increases expression of—and promotes T cell responses to—tumour-associated antigens, delineating a mechanism of infection-induced anti-tumour immunity, which could inform immune-based approaches to cancer treatment.
- Il-Kyu Choi
- , Zhe Wang
- & Baochun Zhang
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Anti-tumour immunity induces aberrant peptide presentation in melanoma
Tryptophan depletion in melanoma cells after prolonged treatment with interferon-γ (IFNγ) results in ribosomal frameshifting and the production of aberrant peptides that can be presented to T cells and induce an immune response.
- Osnat Bartok
- , Abhijeet Pataskar
- & Reuven Agami
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Defining HPV-specific B cell responses in patients with head and neck cancer
Detailed analyses of B cells in the tumour microenvironment of human papilloma virus (HPV)-linked head and neck cancers reveal strong humoral immune responses to HPV antigens and the secretion of HPV-specific antibodies in situ.
- Andreas Wieland
- , Mihir R. Patel
- & Rafi Ahmed
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TGF-β suppresses type 2 immunity to cancer
Depletion of transforming growth factor-β receptor 2 (TGFBR2) in CD4+ T cells results in IL-4-dependent vascular remodelling, stopping tumour growth in a transgenic mouse model of breast cancer, suggesting that type 2 immunity could be targeted for cancer treatments.
- Ming Liu
- , Fengshen Kuo
- & Ming O. Li
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Cancer immunotherapy via targeted TGF-β signalling blockade in TH cells
4T-Trap, a bispecific molecule designed to recognize CD4 and bind TGF-β, blocks TGF-β signalling in T helper cells, causing interleukin-4-dependent vascular reorganization and cancer cell death in a mouse model of breast cancer.
- Shun Li
- , Ming Liu
- & Ming O. Li
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Review Article |
Host–microbiota maladaptation in colorectal cancer
This Review describes the interplay between host genetics, host immunity and the gut microbiome in the modulation of colorectal cancer, and discusses the role of specific bacterial species and metabolites alongside technological advances that will facilitate more in-depth investigation of the microbiome in disease.
- Alina Janney
- , Fiona Powrie
- & Elizabeth H. Mann
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Cancer SLC43A2 alters T cell methionine metabolism and histone methylation
Expression of the transporter SLC43A2 by tumour cells allows them to outcompete T cells for methionine and thereby disrupt the survival and function of tumour-infiltrating T cells.
- Yingjie Bian
- , Wei Li
- & Weiping Zou
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Article |
cDC1 prime and are licensed by CD4+ T cells to induce anti-tumour immunity
Conventional type 1 dendritic cells perform antigen processing and priming of CD4+ and CD8+ T cells against tumour antigens, orchestrating their cross-talk to effect anti-tumour immunity.
- Stephen T. Ferris
- , Vivek Durai
- & Kenneth M. Murphy
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IL-18BP is a secreted immune checkpoint and barrier to IL-18 immunotherapy
An engineered version of IL-18 that is resistant to binding by the soluble decoy receptor IL-18BP shows strong anti-tumour activity in mouse models of cancer.
- Ting Zhou
- , William Damsky
- & Aaron M. Ring
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CRISPR screen in regulatory T cells reveals modulators of Foxp3
A CRISPR-based screening platform was used to identify previously uncharacterized genes that regulate the regulatory T cell-specific master transcription factor Foxp3, indicating that this screening method may be broadly applicable for the discovery of other genes involved in autoimmunity and immune responses to cancer.
- Jessica T. Cortez
- , Elena Montauti
- & Deyu Fang
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Autophagy promotes immune evasion of pancreatic cancer by degrading MHC-I
Inhibition of the autophagy–lysosome system upregulates surface expression of MHC class I proteins and enhances antigen presentation, and evokes a potent anti-tumour immune response that is mediated by CD8+ T cells.
- Keisuke Yamamoto
- , Anthony Venida
- & Alec C. Kimmelman
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A conserved dendritic-cell regulatory program limits antitumour immunity
After taking up tumour-associated antigens, dendritic cells in mouse and human tumours upregulate a regulatory gene program that limits dendritic cell immunostimulatory function, and modulating this program can rescue antitumor immunity in mice.
- Barbara Maier
- , Andrew M. Leader
- & Miriam Merad
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Article |
Gasdermin E suppresses tumour growth by activating anti-tumour immunity
The gasdermin E protein is shown to act as a tumour suppressor: it is cleaved by caspase 3 and granzyme B and leads to pyroptosis of cancer cells, provoking an immune response to the tumour.
- Zhibin Zhang
- , Ying Zhang
- & Judy Lieberman
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A bioorthogonal system reveals antitumour immune function of pyroptosis
In mouse models of cancer, a biorthogonal chemical system based on desilylation catalysed by phenylalanine trifluoroborate enables the controlled release of gasdermin to induce pyroptosis selectively in tumour cells
- Qinyang Wang
- , Yupeng Wang
- & Zhibo Liu
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Article |
Peripheral T cell expansion predicts tumour infiltration and clinical response
Large-scale single-cell sequencing of RNA and T cell receptors in samples from patients with cancer shows clonotypic expansion of effector-like T cells not only in tumour tissue but also in normal adjacent tissues and peripheral blood, which associates with clinical response to cancer immunotherapy.
- Thomas D. Wu
- , Shravan Madireddi
- & Jane L. Grogan
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Article |
ILC2s amplify PD-1 blockade by activating tissue-specific cancer immunity
Tumour-infiltrating group 2 innate lymphoid cells prime CD8+ T cells and amplify the anti-tumour effects of PD-1 blockade in pancreatic ductal adenocarcinoma.
- John Alec Moral
- , Joanne Leung
- & Vinod P. Balachandran
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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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Targeting REGNASE-1 programs long-lived effector T cells for cancer therapy
CRISPR–Cas9 mutagenesis screenings reveal that targeting REGNASE-1 leads to improved therapeutic efficacy of CD8+ T cells against mouse models of cancer, and identify BATF as a key target of REGNASE-1.
- Jun Wei
- , Lingyun Long
- & Hongbo Chi
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Article |
MHC-II neoantigens shape tumour immunity and response to immunotherapy
In a mouse tumour model, immunotherapy-induced rejection of tumour cells requires presentation of both MHC class I and MHC class II antigens, which activate CD4+ and CD8+ T cells, respectively.
- Elise Alspach
- , Danielle M. Lussier
- & Robert D. Schreiber
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Article |
VISTA is an acidic pH-selective ligand for PSGL-1
V-domain immunoglobulin suppressor of T cell activation (VISTA) selectively engages P-selectin glycoprotein ligand-1 (PSGL-1) and suppresses T cells at acidic pH similar to those in tumour microenvironments, thereby mediating resistance to anti-tumour immune responses.
- Robert J. Johnston
- , Linhui Julie Su
- & Alan J. Korman
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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 |
CD24 signalling through macrophage Siglec-10 is a target for cancer immunotherapy
CD24 interacts with the tumour-associated-macrophage receptor Siglec-10 to inhibit the macrophage-mediated clearance of cancer cells, revealing a new ‘don’t eat me’ signal as a potential target for cancer immunotherapy.
- Amira A. Barkal
- , Rachel E. Brewer
- & Irving L. Weissman
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Letter |
Absence of NKG2D ligands defines leukaemia stem cells and mediates their immune evasion
Leukaemic stem cells in acute myeloid leukaemia are defined by a lack of expression of NKG2D ligands, which mediates their ability to evade surveillance by NK cells.
- Anna M. Paczulla
- , Kathrin Rothfelder
- & Claudia Lengerke
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Letter |
TOX is a critical regulator of tumour-specific T cell differentiation
The nuclear factor TOX is highly expressed in antigen-specific dysfunctional T cells in tumours and exhausted T cells during chronic viral infection and is a crucial regulator of the differentiation of tumour-specific T cells.
- Andrew C. Scott
- , Friederike Dündar
- & Andrea Schietinger
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Letter |
Targeting the CBM complex causes Treg cells to prime tumours for immune checkpoint therapy
Disruption of the CARMA1–BCL10–MALT1 (CBM) signalosome causes Treg cells to produce IFNγ and develop dominant anti-tumour activity in synergy with anti-PD-1 treatment, and in the absence of autoimmunity.
- Mauro Di Pilato
- , Edward Y. Kim
- & Thorsten R. Mempel
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Letter |
Prophylactic TNF blockade uncouples efficacy and toxicity in dual CTLA-4 and PD-1 immunotherapy
In mice, prophylactic administration of TNF inhibitors mitigates some of the immune-related adverse effects of immune checkpoint blockade treatment, and also improves to some extent the anti-tumour effect of this immunotherapy.
- Elisabeth Perez-Ruiz
- , Luna Minute
- & Ignacio Melero
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Letter |
CD8+ T cells regulate tumour ferroptosis during cancer immunotherapy
Interferon-γ induces ferroptotic cell death in tumours by suppressing cystine uptake and promoting lipid peroxidation.
- Weimin Wang
- , Michael Green
- & Weiping Zou
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Article |
Fatty acid transport protein 2 reprograms neutrophils in cancer
The lipid transporter FATP2 reprograms neutrophils to polymorphonuclear myeloid-derived suppressor cells by mediating the uptake of arachidonic acid and promoting the synthesis of prostaglandin E2.
- Filippo Veglia
- , Vladimir A. Tyurin
- & Dmitry I. Gabrilovich
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Letter |
CAR T cell trogocytosis and cooperative killing regulate tumour antigen escape
Chimeric antigen receptors (CARs) promote antigen loss in tumour cells by trogocytosis, which results in T cell fratricide killing and exhaustion but can be counteracted by cooperative killing and combinatorial targeting.
- Mohamad Hamieh
- , Anton Dobrin
- & Michel Sadelain
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Letter |
NR4A transcription factors limit CAR T cell function in solid tumours
Transfer of NR4A-deficient T cells expressing chimeric antigen receptors is shown to reduce tumour burden and increase survival by shifting T cell transcriptional programs away from exhaustion and towards increased effector function.
- Joyce Chen
- , Isaac F. López-Moyado
- & Anjana Rao
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Letter |
Anti-tumour immunity controlled through mRNA m6A methylation and YTHDF1 in dendritic cells
The m6A reader protein YTHDF1 suppresses the clearance of tumour cells by enhancing the translation of lysosomal proteases in dendritic cells and thereby suppressing tumour antigen presentation.
- Dali Han
- , Jun Liu
- & Chuan He
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Letter |
Tissue-resident memory CD8+ T cells promote melanoma–immune equilibrium in skin
A transplantable mouse model of persistent cutaneous melanoma shows that immune-mediated tumour suppression can result in a state of melanoma–immune equilibrium, and that tissue-resident memory T cells are essential drivers of this equilibrium state.
- Simone L. Park
- , Anthony Buzzai
- & Thomas Gebhardt
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Letter |
Neoantigen vaccine generates intratumoral T cell responses in phase Ib glioblastoma trial
Neoantigen-targeting vaccines are a feasible therapy for tumours with a low mutation burden and immunologically ‘cold’ tumour microenvironment, as neoantigen-specific T cells from the peripheral blood migrate into intracranial glioblastoma, thereby altering the immune milieu of the glioblastoma.
- Derin B. Keskin
- , Annabelle J. Anandappa
- & David A. Reardon
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Loss of ADAR1 in tumours overcomes resistance to immune checkpoint blockade
Deletion of the A-to-I double-stranded RNA-editing enzyme ADAR1 sensitizes tumour cells to immunotherapy.
- Jeffrey J. Ishizuka
- , Robert T. Manguso
- & W. Nicholas Haining
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Letter |
Disruption of a self-amplifying catecholamine loop reduces cytokine release syndrome
Atrial natriuretic peptide, an anti-inflammatory protein, can protect against cytokine release syndrome induced by therapeutic agents such as tumour-targeting bacteria and CAR-T cells by blocking catecholamine synthesis by macrophages.
- Verena Staedtke
- , Ren-Yuan Bai
- & Shibin Zhou
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Letter |
FBXO38 mediates PD-1 ubiquitination and regulates anti-tumour immunity of T cells
PD-1 undergoes internalization, FBXO38-mediated ubiquitination and proteasome degradation in activated T cells, and inhibition of this pathway dampens anti-tumour immunity of T cells.
- Xiangbo Meng
- , Xiwei Liu
- & Chenqi Xu
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Letter |
Design of amidobenzimidazole STING receptor agonists with systemic activity
A small-molecule agonist for the cGAS–STING pathway has systemic activity in a mouse model of colon cancer.
- Joshi M. Ramanjulu
- , G. Scott Pesiridis
- & John Bertin