Featured
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Letter |
LILRB4 signalling in leukaemia cells mediates T cell suppression and tumour infiltration
The receptor LILRB4 on monocytic leukaemia cells suppresses T cell activity and support the infiltration of tumour cells into tissues.
- Mi Deng
- , Xun Gui
- & Cheng Cheng Zhang
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Letter |
IRE1α–XBP1 controls T cell function in ovarian cancer by regulating mitochondrial activity
In human and mouse models of ovarian cancer, endoplasmic reticulum stress and the activation of the IRE1α–XBP1 pathway decreases the metabolic fitness of T cells and limits their anti-tumour functions.
- Minkyung Song
- , Tito A. Sandoval
- & Juan R. Cubillos-Ruiz
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Article |
A homing system targets therapeutic T cells to brain cancer
Therapeutic T cells bearing ligands engineered to optimize adhesion and transmigration through the blood–brain barrier can be targeted to brain tumours.
- Heba Samaha
- , Antonella Pignata
- & Nabil Ahmed
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Letter |
Exosomal PD-L1 contributes to immunosuppression and is associated with anti-PD-1 response
Melanoma cells release programmed death-ligand 1 (PD-L1) on the surface of circulating exosomes, suggesting a mechanism by which tumours could evade the immunesystem, and the potential application of exosomal PD-L1 to monitor patient responses to checkpoint therapies.
- Gang Chen
- , Alexander C. Huang
- & Wei Guo
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Article |
IL-23 secreted by myeloid cells drives castration-resistant prostate cancer
IL-23 produced by myeloid-derived suppressor cells regulates castration resistance in prostate cancer by sustaining androgen receptor signalling.
- Arianna Calcinotto
- , Clarissa Spataro
- & Andrea Alimonti
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Letter |
Induction and transcriptional regulation of the co-inhibitory gene module in T cells
A module of co-inhibitory T cell receptors, driven by the cytokine IL-27, is identified in mice that is regulated by the transcription factors PRDM1 and c-MAF.
- Norio Chihara
- , Asaf Madi
- & Vijay K. Kuchroo
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Letter |
Disruption of TET2 promotes the therapeutic efficacy of CD19-targeted T cells
Genetically engineered T cells that induced remission in a patient with chronic lymphocytic leukaemia were found to have disruption of the TET2 gene, which caused T cell changes that potentiated their anti-tumour effects.
- Joseph A. Fraietta
- , Christopher L. Nobles
- & J. Joseph Melenhorst
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Letter |
Bystander CD8+ T cells are abundant and phenotypically distinct in human tumour infiltrates
Human lung and colorectal tumours contain a population of tumour-infiltrating lymphocytes that are specific for tumour-unrelated antigens and, unlike tumour-antigen-specific tumour-infiltrating lymphocytes, do not express CD39.
- Yannick Simoni
- , Etienne Becht
- & Evan W. Newell
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Letter |
TGFβ drives immune evasion in genetically reconstituted colon cancer metastasis
A combination of TGFβ inhibition and checkpoint-inhibition therapy provokes a potent cytotoxic response against metastatic tumours derived from colorectal cancers in mice.
- Daniele V. F. Tauriello
- , Sergio Palomo-Ponce
- & Eduard Batlle
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Letter |
Runx3 programs CD8+ T cell residency in non-lymphoid tissues and tumours
The transcription factor Runx3 is identified as a central regulator of the development of tissue-resident memory CD8+ T cells, providing insights into the signals that promote T cell residency in non-lymphoid tissues and tumours.
- J. Justin Milner
- , Clara Toma
- & Ananda W. Goldrath
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Letter |
Cyclin D–CDK4 kinase destabilizes PD-L1 via cullin 3–SPOP to control cancer immune surveillance
Abundance of PD-L1, the ligand of the anti-cancer immunotherapy target PD-1, is negatively regulated by poly-ubiquitination via the cyclin D–CDK4/cullin 3–SPOP axis and PD-1 blockade treatment in mice improved survival when combined with CDK4/6 inhibitors.
- Jinfang Zhang
- , Xia Bu
- & Wenyi Wei
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Article |
Inflammation-induced IgA+ cells dismantle anti-liver cancer immunity
IgA+ B cells expressing programmed death ligand 1 (PD-L1) and interleukin 10 accumulate in the inflamed livers of humans and mice with non-alcoholic fatty liver disease where they promote the progression to hepatocellular carcinoma by limiting the local activation of PD-1-expressing CD8+ T cells.
- Shabnam Shalapour
- , Xue-Jia Lin
- & Michael Karin
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Letter |
Identification of unique neoantigen qualities in long-term survivors of pancreatic cancer
The analysis of T-cell antigens in long-term survivors of pancreatic ductal adenocarcinoma suggests that neoantigen immunogenicity and quality, not purely quantity, correlate with survival.
- Vinod P. Balachandran
- , Marta Łuksza
- & Steven D. Leach
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Letter |
IL-1R8 is a checkpoint in NK cells regulating anti-tumour and anti-viral activity
Interleukin-1 receptor 8 (IL-1R8), a negative regulator of the IL-1 family of cytokines, restrains the activity of natural killer (NK) cells, suggesting that IL-1R8 acts as a checkpoint regulator of NK cell activation and that its blockade may be of use in cancer therapy.
- Martina Molgora
- , Eduardo Bonavita
- & Alberto Mantovani
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Letter |
CDK4/6 inhibition triggers anti-tumour immunity
Mouse models of breast carcinoma and other solid tumours show that selective cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors not only induce tumour cell cycle arrest but also promote anti-tumour immunity.
- Shom Goel
- , Molly J. DeCristo
- & Jean J. Zhao
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Letter |
CMTM6 maintains the expression of PD-L1 and regulates anti-tumour immunity
CMTM6 maintains PD-L1 at the plasma membrane by inhibiting its lysosome-mediated degradation and promoting its recycling.
- Marian L. Burr
- , Christina E. Sparbier
- & Mark A. Dawson
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Letter |
cGAS surveillance of micronuclei links genome instability to innate immunity
The cytoplasmic DNA sensor cGAS detects DNA in ruptured micronuclei and activates an innate immune response.
- Karen J. Mackenzie
- , Paula Carroll
- & Andrew P. Jackson
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Article |
In vivo CRISPR screening identifies Ptpn2 as a cancer immunotherapy target
In vivo CRISPR screening reveals that loss of Ptpn2 increases the response of tumour cells to immunotherapy and increases IFNγ signalling, suggesting that PTPN2 inhibition may potentiate the effect of immunotherapies that invoke an IFNγ response.
- Robert T. Manguso
- , Hans W. Pope
- & W. Nicholas Haining
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Letter |
An immunogenic personal neoantigen vaccine for patients with melanoma
The results of a phase I trial assessing a personal neoantigen multi-peptide vaccine in patients with melanoma, showing feasibility, safety, and immunogenicity.
- Patrick A. Ott
- , Zhuting Hu
- & Catherine J. Wu
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Review Article |
Therapeutic T cell engineering
The use of genetically engineered T cells in the treatment of cancer is reviewed, with particular focus on anti-CD19 chimaeric antigen receptor therapy, providing a summary of past progress and current status, and potential future directions.
- Michel Sadelain
- , Isabelle Rivière
- & Stanley Riddell
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Letter |
PD-1 expression by tumour-associated macrophages inhibits phagocytosis and tumour immunity
Mouse and human tumour-associated macrophages express PD-1, which increases with cancer stage and induces decreased phagocytosis by macrophages; by contrast, PD-L1 removal increases phagocytosis in vivo, decreases tumour burden and increases survival of mice.
- Sydney R. Gordon
- , Roy L. Maute
- & Irving L. Weissman
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Article |
Chromatin states define tumour-specific T cell dysfunction and reprogramming
Epigenetic programming of T cells in solid tumours from a functional to a dysfunctional state occurs in two phases, and only the first phase is reversible.
- Mary Philip
- , Lauren Fairchild
- & Andrea Schietinger
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Letter |
Tumour ischaemia by interferon-γ resembles physiological blood vessel regression
Interferon-γ acts on tumour endothelial cells to drive vascular regression, inducing ischaemia that leads to tumour collapse.
- Thomas Kammertoens
- , Christian Friese
- & Thomas Blankenstein
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Article |
T-cell invigoration to tumour burden ratio associated with anti-PD-1 response
The clinical benefit of anti-PD-1 antibody treatment is dependent on the extent to which exhausted CD8 T cells are reinvigorated in relation to the tumour burden of the patient.
- Alexander C. Huang
- , Michael A. Postow
- & E. John Wherry
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Letter |
Mutual regulation of tumour vessel normalization and immunostimulatory reprogramming
The cross-talk between immune cells and blood vessel endothelial cells promotes pericyte coverage and decreases hypoxia in mouse tumour models, and correlative evidence suggests that these processes influence cancer prognosis in humans.
- Lin Tian
- , Amit Goldstein
- & Xiang H.-F. Zhang
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Letter |
Antigen presentation profiling reveals recognition of lymphoma immunoglobulin neoantigens
Evidence for the abundant presentation of class II neoantigens by a human B-cell lymphoma.
- Michael S. Khodadoust
- , Niclas Olsson
- & Ash A. Alizadeh
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Letter |
Class IIa HDAC inhibition reduces breast tumours and metastases through anti-tumour macrophages
A selective class IIa histone deacetylase inhibitor induces anti-tumour immunity in a mouse model of mammary cancer through altered differentiation and recruitment of tumour-associated macrophages.
- Jennifer L. Guerriero
- , Alaba Sotayo
- & Anthony Letai
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Letter |
Genome-wide in vivo screen identifies novel host regulators of metastatic colonization
Screening mutant mouse lines using a genome-wide in vivo assay identifies microenvironmental regulators of metastatic colonization and defines SPNS2 as an important mediator of lung colonization.
- Louise van der Weyden
- , Mark J. Arends
- & David J. Adams
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Letter |
PI3Kγ is a molecular switch that controls immune suppression
Modulation of PI3Kγ activity regulates macrophage polarization during inflammation and cancer, whilst combining PI3Kγ inhibition with immune checkpoint inhibitors leads to synergistic tumour-inhibitory effects.
- Megan M. Kaneda
- , Karen S. Messer
- & Judith A. Varner
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Letter |
Ionic immune suppression within the tumour microenvironment limits T cell effector function
Potassium ions released by necrotic cells in tumours impair T cell function by increasing the intracellular potassium concentration in vitro and in vivo.
- Robert Eil
- , Suman K. Vodnala
- & Nicholas P. Restifo
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Letter |
Aberrant PD-L1 expression through 3′-UTR disruption in multiple cancers
Structural variations disrupting the 3′ region of PD-L1 are shown to aid immune evasion in a number of human cancers, including adult T-cell leukaemia/lymphoma, and in a mouse tumour model, CRISPR/Cas9-mediated deletion of the 3'-UTR of Pd-l1 is also shown to result in immune escape, suggesting that PD-L1 3′-UTR disruption could provide a diagnostic marker to identify patients who will benefit from anti-PD-1/PD-L1 therapy.
- Keisuke Kataoka
- , Yuichi Shiraishi
- & Seishi Ogawa
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Letter |
The necrosome promotes pancreatic oncogenesis via CXCL1 and Mincle-induced immune suppression
A study of pancreatic ductal adenocarcinoma shows that cancer cell proliferation is associated with increased expression of proteins that control programmed necrotic cell death and suppress the adaptive immune system.
- Lena Seifert
- , Gregor Werba
- & George Miller
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Letter |
Visualization of immediate immune responses to pioneer metastatic cells in the lung
Tracing the fate of circulating tumour cells by intravital two-photon lung imaging shows that tumours produce microparticles as they arrive and these migrate along the lung vasculature and are mostly taken up by interstitial myeloid cells, in a process that contributes to metastatic seeding; a minor subset of microparticles is engulfed by conventional dendritic cells, which are thought to contribute to the initiation of an anti-tumour immune response in lung-draining lymph nodes.
- Mark B. Headley
- , Adriaan Bins
- & Matthew F. Krummel
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Letter |
Potentiating the antitumour response of CD8+ T cells by modulating cholesterol metabolism
Modulating cholesterol metabolism can improve CD8+ T-cell-mediated immunity against tumours; genetic or pharmacological inhibition of the cholesterol esterification enzyme ACAT1 led to higher plasma membrane cholesterol levels, better T-cell receptor clustering and signalling, improved immunological synapse maturation, and enhanced antitumour activity in mice.
- Wei Yang
- , Yibing Bai
- & Chenqi Xu
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Letter |
NAFLD causes selective CD4+ T lymphocyte loss and promotes hepatocarcinogenesis
Non-alcoholic fatty liver disease (NAFLD) is shown to promote hepatocellular carcinoma through the generation of linoleic acid, disruption of mitochondrial function and selective loss of CD4+ T cells, leading to impaired anti-tumour immunity.
- Chi Ma
- , Aparna H. Kesarwala
- & Tim F. Greten
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Letter |
Graded Foxo1 activity in Treg cells differentiates tumour immunity from spontaneous autoimmunity
The transcription factor Foxo1 is shown to be involved in the determination of distinct subsets of regulatory T (Treg) cells, and the differentiation of activated phenotype Treg cells is associated with the repression of the Foxo1-dependent transcriptional program; constitutively active Foxo1 expression triggers depletion of activated Treg cells in peripheral tissues and leads to CD8 T-cell-mediated autoimmunity and anti-tumour immunity.
- Chong T. Luo
- , Will Liao
- & Ming O. Li
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Letter |
Epigenetic silencing of TH1-type chemokines shapes tumour immunity and immunotherapy
Treating ovarian cancer in mouse models with inhibitors for the epigenetic regulators EZH2 and DNMT1 increases the expression of the inflammatory chemokines CXCL9 and CXCL10, resulting in enhanced tumour infiltration by effector T cells, and slowed tumour progression.
- Dongjun Peng
- , Ilona Kryczek
- & Weiping Zou
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Letter |
Melanoma-intrinsic β-catenin signalling prevents anti-tumour immunity
Only a subset of patients with melanoma responds to new immunotherapeutic therapies; here, β-catenin signalling is identified as an important pathway that confers resistance to this type of approach, with implications for future treatment strategies.
- Stefani Spranger
- , Riyue Bao
- & Thomas F. Gajewski
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Letter |
Allogeneic IgG combined with dendritic cell stimuli induce antitumour T-cell immunity
Naturally occurring tumour-binding IgG antibodies are shown to initiate the rejection of allogeneic tumours, whereby Fc-receptor-mediated uptake of tumour immune complexes into dendritic cells activates tumour-reactive T cells, and intra-tumoral injection of allogeneic IgG together with dendritic cell adjuvants induces systemic T-cell-mediated antitumour responses.
- Yaron Carmi
- , Matthew H. Spitzer
- & Edgar G. Engleman
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Letter |
Immunosuppressive plasma cells impede T-cell-dependent immunogenic chemotherapy
IgA plasmocytes are shown to promote resistance to the immunogenic chemotherapeutic oxaliplatin in prostate cancer mouse models by inhibiting activation of cytotoxic T cells; immunosuppressive plasma cells, which are also found in human-therapy-resistant prostate cancer, are generated in response to TGFβ, and their functionality depends on PD-L1 expression and IL-10 secretion.
- Shabnam Shalapour
- , Joan Font-Burgada
- & Michael Karin
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Letter |
IL-17-producing γδ T cells and neutrophils conspire to promote breast cancer metastasis
Tumours maximize their chance of metastasizing by evoking a systemic inflammatory cascade in mouse models of spontaneous breast cancer metastasis.
- Seth B. Coffelt
- , Kelly Kersten
- & Karin E. de Visser
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Letter |
Radiation and dual checkpoint blockade activate non-redundant immune mechanisms in cancer
In this study, involving melanoma patients and a mouse model for melanoma, an optimal anti-tumour response was induced by using a combination of radiation with anti-CTLA4 and anti-PD-L1 antibody therapies, each attacking the tumour from a different angle.
- Christina Twyman-Saint Victor
- , Andrew J. Rech
- & Andy J. Minn
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Letter |
Predicting immunogenic tumour mutations by combining mass spectrometry and exome sequencing
A combination of genome-wide exome and transcriptome analysis, mass spectrometry and computational structural modelling are used here to identify immunogenic neo-antigens in two mouse tumour cancer cell lines; mice vaccinated with predicted immunogenic peptides yielded therapeutically useful cytotoxic T-lymphocyte responses.
- Mahesh Yadav
- , Suchit Jhunjhunwala
- & Lélia Delamarre
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Letter |
PD-1 blockade induces responses by inhibiting adaptive immune resistance
The dynamics of T-cell responses are investigated in tumour tissue from patients with advanced melanoma who were treated with a PD-1-blocking monoclonal antibody, revealing that clinical efficacy of the treatment correlates with increased frequencies of pre-existing CD8+ T cells and PD-1 and PD-L1 expression.
- Paul C. Tumeh
- , Christina L. Harview
- & Antoni Ribas
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Letter |
Tumour-infiltrating Gr-1+ myeloid cells antagonize senescence in cancer
Senescence in cancer can be antagonized by a subset of immune cells acting in a non-cell-autonomous manner.
- Diletta Di Mitri
- , Alberto Toso
- & Andrea Alimonti
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Letter |
A vaccine targeting mutant IDH1 induces antitumour immunity
The mutant IDH1 protein, which is expressed in a large fraction of human gliomas, is shown to be immunogenic; mutant-specific immune responses can be detected in patients with IDH1 mutated gliomas and generated in mice and are shown to treat established IDH1 mutant tumours in a syngeneic MHC humanized mouse model in a CD4 T-cell-dependent manner.
- Theresa Schumacher
- , Lukas Bunse
- & Michael Platten
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Letter |
Inactivation of PI(3)K p110δ breaks regulatory T-cell-mediated immune tolerance to cancer
The kinase PI(3)Kδ is shown to be required for the immunosuppressive function of regulatory T cells; inactivation of PI(3)Kδ in these cells leads to enhanced cytotoxic T-cell function and restricts tumour growth and metastasis in a variety of mouse tumour models.
- Khaled Ali
- , Dalya R. Soond
- & Bart Vanhaesebroeck
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Letter |
The E3 ligase Cbl-b and TAM receptors regulate cancer metastasis via natural killer cells
The E3 ligase Cbl-b acts on TAM tyrosine kinase receptors and has a critical role in the regulation of natural killer (NK) cell rejection of metastatic tumours; a small molecule TAM kinase inhibitor is shown to enhance the anti-metastatic NK cell activity.
- Magdalena Paolino
- , Axel Choidas
- & Josef M. Penninger
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Letter |
Adenoma-linked barrier defects and microbial products drive IL-23/IL-17-mediated tumour growth
In a mouse model of colorectal cancer, barrier deterioration results in adenoma invasion by microbial products that trigger tumour-elicited inflammation, which in turn drives IL-23-dependent tumour growth.
- Sergei I. Grivennikov
- , Kepeng Wang
- & Michael Karin