Featured
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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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Review Article |
Harnessing innate immunity in cancer therapy
The authors review recent developments in our understanding of the antitumour effects of the innate immune system and how this system could be harnessed in the clinic.
- Olivier Demaria
- , Stéphanie Cornen
- & Eric Vivier
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Article |
Dynamics and genomic landscape of CD8+ T cells undergoing hepatic priming
CD8+ T cells that are primed by hepatocytes differentiate into dysfunctional T cells, which can be rescued by treatment with IL-2.
- Alexandre P. Bénéchet
- , Giorgia De Simone
- & Matteo Iannacone
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Letter |
SLC19A1 transports immunoreactive cyclic dinucleotides
A genome-wide CRISPR-interference screen is used to identify the reduced folate carrier SLC19A1 as the major transporter of cyclic dinucleotides in human cells, with potential roles in immunotherapeutic treatment of cancer, immune responses to pathogens and inflammatory diseases.
- Rutger D. Luteijn
- , Shivam A. Zaver
- & David H. Raulet
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Letter |
Targeting cardiac fibrosis with engineered T cells
Adoptive transfer of CAR T cells against the fibroblast marker FAP reduces cardiac fibrosis and restores function after cardiac injury in mice, providing proof-of-principle for the development of immunotherapeutic treatments for cardiac disease.
- Haig Aghajanian
- , Toru Kimura
- & Jonathan A. Epstein
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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 |
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 |
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 |
The metabolite BH4 controls T cell proliferation in autoimmunity and cancer
Tetrahydrobiopterin (BH4) is an enzyme co-factor that is involved in the nervous system; it is shown here to also function in T cell activation and proliferation, with roles in autoimmunity, allergic inflammation and cancer.
- Shane J. F. Cronin
- , Corey Seehus
- & Josef M. Penninger
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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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Article |
Combination therapy with anti-HIV-1 antibodies maintains viral suppression
Combination therapy with the anti-HIV-1 monoclonal antibodies 3BNC117 and 10-1074 maintains long-term suppression in the absence of antiretroviral therapy in individuals with antibody-sensitive viral reservoirs.
- Pilar Mendoza
- , Henning Gruell
- & Michel C. Nussenzweig
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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 |
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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Review Article |
The biology and management of non-small cell lung cancer
- Roy S. Herbst
- , Daniel Morgensztern
- & Chris Boshoff
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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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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 CMTM6 and CMTM4 as PD-L1 protein regulators
CMTM6 and CMTM4 bind to and stabilize the inhibitory receptor PD-L1 and regulate PD-L1 levels at the surface of human tumour and immune cells.
- Riccardo Mezzadra
- , Chong Sun
- & Ton N. M. Schumacher
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Article |
Identification of essential genes for cancer immunotherapy
The authors describe a two-cell-type CRISPR screen to identify tumour-intrinsic genes that regulate the sensitivity of cancer cells to effector T cell function.
- Shashank J. Patel
- , Neville E. Sanjana
- & Nicholas P. Restifo
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Letter |
Personalized RNA mutanome vaccines mobilize poly-specific therapeutic immunity against cancer
The authors report the first-in-human application of personalized neo-antigen RNA vaccines in patients with melanoma.
- Ugur Sahin
- , Evelyna Derhovanessian
- & Özlem Türeci
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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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Letter |
SLAMF7 is critical for phagocytosis of haematopoietic tumour cells via Mac-1 integrin
The identification of homotypic SLAMF7 interactions responsible for haematopoietic tumour cell phagocytosis by macrophages when the inhibitory receptor/ligand interaction of SIRPα/CD47 is blocked therapeutically.
- Jun Chen
- , Ming-Chao Zhong
- & André Veillette
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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 |
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 |
Overcoming resistance to checkpoint blockade therapy by targeting PI3Kγ in myeloid cells
Targeting tumour-infiltrating suppressive myeloid cells with a selective PI3Kγ inhibitor overcomes resistance to checkpoint blockade therapy in various mouse myeloid-rich tumour models.
- Olivier De Henau
- , Matthew Rausch
- & Taha Merghoub
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Letter |
Single-cell RNA-seq identifies a PD-1hi ILC progenitor and defines its development pathway
Single-cell RNA sequencing of bone marrow innate lymphoid cell (ILC) precursors reveals that PD-1 marks a committed ILC progenitor and that ILC2 development requires Bcl11b and IL-25R expression; activated ILCs can also be depleted by a PD-1 antibody.
- Yong Yu
- , Jason C. H. Tsang
- & Pentao Liu
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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 |
Neoantigen landscape dynamics during human melanoma–T cell interactions
Analyses of tumour samples and tumour-infiltrating lymphocytes from two patients with melanoma who were treated with adoptive T-cell therapy provide evidence for tumour escape by loss and downregulation of immunogenic antigens.
- Els M. E. Verdegaal
- , Noel F. C. C. de Miranda
- & Sjoerd H. van der Burg
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Letter |
Systemic RNA delivery to dendritic cells exploits antiviral defence for cancer immunotherapy
The development of a nanoparticle RNA vaccine is reported that preferentially targets dendritic cells after systemic administration, and is shown to provide durable interferon-α-dependent antigen-specific immunity in mouse tumour models; initial results in advanced melanoma patients indicate potential efficacy in humans.
- Lena M. Kranz
- , Mustafa Diken
- & Ugur Sahin
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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 |
Mutant MHC class II epitopes drive therapeutic immune responses to cancer
The authors show that a large fraction of tumour mutations is immunogenic and predominantly recognized by CD4+ T cells; they use these data to design synthetic messenger-RNA-based vaccines specific against tumour mutations, and show that these can reject tumours in mice.
- Sebastian Kreiter
- , Mathias Vormehr
- & Ugur Sahin
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Letter |
Tetanus toxoid and CCL3 improve dendritic cell vaccines in mice and glioblastoma patients
A clinical trial in patients with glioblastoma shows increased immune and anti-tumour responses to dendritic cell vaccination after pre-conditioning the site of vaccination with tetanus toxoid (Td); similar results are also seen in mice in part due to the actions of the chemokine CCL3, and the findings may represent new ways to improve the efficacy of anti-cancer vaccines.
- Duane A. Mitchell
- , Kristen A. Batich
- & John H. Sampson
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Letter |
Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients
Clinical and correlative biomarker results from a phase 1 clinical trial in patients with different solid tumours are presented; the findings indicate that PD-L1 expression on tumour-infiltrating immune cells is associated with clinical response to MPDL3280A (anti-PD-L1).
- Roy S. Herbst
- , Jean-Charles Soria
- & F. Stephen Hodi
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Letter |
MPDL3280A (anti-PD-L1) treatment leads to clinical activity in metastatic bladder cancer
The results of a clinical phase I study in metastatic urothelial bladder cancer treated with the MPDL3280A antibody show that expression of PD-L1 on tumour-infiltrating immune cells is relevant for the therapeutic response.
- Thomas Powles
- , Joseph Paul Eder
- & Nicholas J. Vogelzang
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Letter |
Checkpoint blockade cancer immunotherapy targets tumour-specific mutant antigens
A carcinogen-induced mouse tumour model is used here to show that mutant tumour-specific antigens are targets for CD8+ T-cell responses, mediating tumour regression after checkpoint blockade immunotherapy, and that these antigens can be used effectively in therapeutic vaccines; this advance potentially opens the door to personalized cancer vaccines.
- Matthew M. Gubin
- , Xiuli Zhang
- & Robert D. Schreiber
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Article |
Reversion of advanced Ebola virus disease in nonhuman primates with ZMapp
A new treatment, containing an optimized cocktail of three monoclonal antibodies against Ebola virus, provided full protection and disease reversal in rhesus monkeys when given under conditions in which controls succumbed by day 8; this new therapy may be a good candidate for treating Ebola virus infection in human patients.
- Xiangguo Qiu
- , Gary Wong
- & Gary P. Kobinger
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Outlook |
The age of vaccines
The advent of routine childhood vaccination has led to dramatic declines in many contagious diseases in the United States. Maintaining these gains there and spreading these successes worldwide are major public-health challenges. By Tony Scully.
- Tony Scully
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Outlook |
Production: Vaccines from the East
China is poised to become a major global vaccine maker, but first it must overcome serious problems with quality control.
- Priya Shetty
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Outlook |
Polio: The eradication endgame
Researchers are developing a strategy that could put an end to polio forever.
- Cassandra Willyard
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Outlook |
Logistics: Keeping cool
Extreme temperatures damage vaccines. Efforts are underway to find better ways to deliver the goods.
- Neil Savage
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Outlook |
Perspective: Elimination round
We must push harder to eliminate diseases, for everyone's benefit, say Andrew Artenstein and Gregory Poland.
- Andrew W. Artenstein
- & Gregory A. Poland
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Outlook |
Perspective: Ill prepared for a pandemic
Klaus Stöhr asks whether those responsible for public health will grasp new opportunities to ensure pandemic vaccine readiness.
- Klaus Stöhr
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Outlook |
Public health: An injection of trust
Faced with outbreaks of preventable diseases, public-health experts need to win over parents who refuse vaccinations.
- Michael Eisenstein
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Article |
In vivo discovery of immunotherapy targets in the tumour microenvironment
A short hairpin RNA screen to identify genes that modify the action of tumour-infiltrating CD8 T cells in tumour-bearing mice pinpointed the phosphatase subunit Ppp2r2d as a new target for tumour therapy; knockdown of Ppp2r2d in T cells enabled their accumulation in tumours and significantly delayed tumour growth.
- Penghui Zhou
- , Donald R. Shaffer
- & Kai W. Wucherpfennig
c-Jun overexpression in CAR T cells induces exhaustion resistance