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PGE2 limits effector expansion of tumour-infiltrating stem-like CD8+ T cells
Tumour-derived prostaglandin E2, signaling through its receptors EP2 and EP4, is shown to restrain the responses of tumour-infiltrating stem-like TCF1+CD8+ T lymphocytes, and modulation of T cell EP2 and EP4 can restore anticancer immunity.
- Sebastian B. Lacher
- , Janina Dörr
- & Jan P. Böttcher
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FOXO1 enhances CAR T cell stemness, metabolic fitness and efficacy
Increased effectiveness of anti-cancer chimeric antigen receptor T cell therapy is associated with a stem-like phenotype through increased expression of FOXO1.
- Jack D. Chan
- , Christina M. Scheffler
- & Phillip K. Darcy
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SOX17 enables immune evasion of early colorectal adenomas and cancers
Transcriptomic and chromatin accessibility analyses of naive and transplanted colon cancer organoids in a mouse model reveal a key role for the transcription factor SOX17 in establishing a permissive immune environment for tumour cells.
- Norihiro Goto
- , Peter M. K. Westcott
- & Ömer H. Yilmaz
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The nuclear factor ID3 endows macrophages with a potent anti-tumour activity
The Kupffer cell lineage-determining factor ID3 selectively endows macrophages with the ability to phagocytose live tumour cells and orchestrate the recruitment, proliferation and activation of natural killer and CD8+ T lymphoid effector cells to restrict the growth of a variety of tumours.
- Zihou Deng
- , Pierre-Louis Loyher
- & Frederic Geissmann
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Tumour circular RNAs elicit anti-tumour immunity by encoding cryptic peptides
The tumour-specific circular RNA FAM53B is highly immunogenic and can induce anti-tumour responses in mouse models of breast cancer and melanoma, expanding the repertoire of anticancer targets for development.
- Di Huang
- , Xiaofeng Zhu
- & Erwei Song
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An IL-4 signalling axis in bone marrow drives pro-tumorigenic myelopoiesis
Single-cell transcriptomics studies on human and mouse non-small cell lung cancer and conditional knockout mouse models show that IL-4 from bone marrow basophils drives the development of granulocyte-monocyte progenitors to myeloid cells that suppress antitumour immunity.
- Nelson M. LaMarche
- , Samarth Hegde
- & Miriam Merad
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Trans-vaccenic acid reprograms CD8+ T cells and anti-tumour immunity
A screen of nutrient-derived compounds identified trans-vaccenic acid as a promoter of effector T cell function, and functional assays demonstrate that this occurs via inactivation of GPR43 on T cells.
- Hao Fan
- , Siyuan Xia
- & Jing Chen
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Single-cell CRISPR screens in vivo map T cell fate regulomes in cancer
Analyses of causal gene regulatory networks have identified key checkpoints mediating the progressive differentiation of CD8+ cytotoxic T cells, findings that have implications for anticancer immunotherapies such as adoptive cell therapy and immune checkpoint blockade.
- Peipei Zhou
- , Hao Shi
- & Hongbo Chi
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The PTPN2/PTPN1 inhibitor ABBV-CLS-484 unleashes potent anti-tumour immunity
An orally bioavailable small-molecule active-site inhibitor of the phosphatases PTPN2 and PTPN1, ABBV-CLS-484, demonstrates immunotherapeutic efficacy in mouse models of cancer resistant to PD-1 blockade.
- Christina K. Baumgartner
- , Hakimeh Ebrahimi-Nik
- & Robert T. Manguso
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The β1-adrenergic receptor links sympathetic nerves to T cell exhaustion
Stress-associated catecholamines promote CD8+ T cell exhaustion through the β1-adrenergic receptor, and blocking β-adrenergic signalling may help restore anti-tumour functions.
- Anna-Maria Globig
- , Steven Zhao
- & Susan M. Kaech
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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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CRISPR screens decode cancer cell pathways that trigger γδ T cell detection
A combination of genome-wide CRISPR screens in target cancer cells identifies pathways that regulate γδ T cell killing and BTN3A cell surface expression.
- Murad R. Mamedov
- , Shane Vedova
- & Alexander Marson
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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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Interferon-ε is a tumour suppressor and restricts ovarian cancer
Interferon-ε is a tumour suppressor expressed in the epithelial cell of origin of ovarian cancer, which it restricts by direct action on tumour cells and especially by activation of anti-tumour immunity.
- Zoe R. C. Marks
- , Nicole K. Campbell
- & Paul J. Hertzog
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SLC38A2 and glutamine signalling in cDC1s dictate anti-tumour immunity
Competition for glutamine between type-1 conventional dendritic cells and tumour cells has a central role in tuning the anti-tumour immune response and in immune evasion by cancer cells.
- Chuansheng Guo
- , Zhiyuan You
- & Hongbo Chi
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Reprogramming tumour-associated macrophages to outcompete cancer cells
In a mouse model of breast cancer, a low-protein diet induces engulfment activities and mTORC1 signalling in tumour-associated macrophages to suppress engulfment-dependent mTORC1 signalling in MYC-overexpressing cancer cells through cell competition, serving as an innate immune defence mechanism to slow tumour growth.
- Xian Zhang
- , Shun Li
- & Ming O. Li
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B-cell-specific checkpoint molecules that regulate anti-tumour immunity
Manipulation of TIM-1-expressing B cells enables engagement of the second arm of adaptive immunity to promote anti-tumour immunity and inhibit tumour growth.
- Lloyd Bod
- , Yoon-Chul Kye
- & Vijay K. Kuchroo
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Y chromosome loss in cancer drives growth by evasion of adaptive immunity
Loss of the Y chromosome in tumour cells is associated with a poor prognosis for patients with bladder cancer by causing local T cell exhaustion, which also increases the response to immune checkpoint blockade therapy.
- Hany A. Abdel-Hafiz
- , Johanna M. Schafer
- & Dan Theodorescu
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CD4+ T cell-induced inflammatory cell death controls immune-evasive tumours
This article describes a mechanism through which CD4+ T cells can eradicate MHC-deficient tumours that escape direct CD8+ T cell targeting and thereby complement the activity of CD8+ T cells and natural killer cells to advance cancer immunotherapies.
- Bastian Kruse
- , Anthony C. Buzzai
- & Thomas Tüting
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Tumour immune rejection triggered by activation of α2-adrenergic receptors
Agonists of α2-adrenergic receptors could substantially improve the clinical efficacy of cancer immunotherapy.
- Jingjing Zhu
- , Stefan Naulaerts
- & Benoit J. Van den Eynde
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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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Microbial peptides activate tumour-infiltrating lymphocytes in glioblastoma
Tumour-infiltrating lymphocytes from glioblastoma can recognize bacterial and gut microbial peptides.
- Reza Naghavian
- , Wolfgang Faigle
- & Roland Martin
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Targeting PD-L2–RGMb overcomes microbiome-related immunotherapy resistance
Interactions between programmed death ligand 2 (PD-L2) and its binding partner RGMb are downregulated by the gut microbiota, a mechanism that may be exploited to enhance the efficacy of PD-1-based cancer immunotherapies.
- Joon Seok Park
- , Francesca S. Gazzaniga
- & Arlene H. Sharpe
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PI3Kβ controls immune evasion in PTEN-deficient breast tumours
A mouse model of invasive breast cancer in which Pten and Trp53 are simultaneously inactivated links PTEN loss with STAT3 activation and indicates that immune escape in PTEN-null tumours is mediated by PI3Kβ.
- Johann S. Bergholz
- , Qiwei Wang
- & Jean J. Zhao
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Antibodies against endogenous retroviruses promote lung cancer immunotherapy
In lung adenocarcinoma, antibodies against endogenous retroviruses promote anti-tumour activity, and expression of endogenous retroviruses can predict outcomes of immunotherapy.
- Kevin W. Ng
- , Jesse Boumelha
- & George Kassiotis
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Noncoding translation mitigation
Combining genome-wide CRISPR screens with massively parallel analyses of human and random DNA sequences reveal a unified mechanism for the surveillance and evolution of translation products from annotated noncoding DNA.
- Jordan S. Kesner
- , Ziheng Chen
- & Xuebing Wu
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STING inhibits the reactivation of dormant metastasis in lung adenocarcinoma
STING signalling is activated in metastatic cancer cells that exit from an immune-evasive dormant state, blocking their progression and cancer relapse.
- Jing Hu
- , Francisco J. Sánchez-Rivera
- & Joan Massagué
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Neoantigen-targeted CD8+ T cell responses with PD-1 blockade therapy
Effective anti-PD-1 immunotherapy is associated with the presence of polyclonal CD8+ T cells in the tumour and blood specific for a limited number of immunodominant mutations, which are recurrently recognized over time.
- Cristina Puig-Saus
- , Barbara Sennino
- & Antoni Ribas
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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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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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γδ T cells are effectors of immunotherapy in cancers with HLA class I defects
γδ T cells contribute to the response to immune checkpoint blockade treatment in patients with HLA-class-I-negative DNA mismatch repair-deficient colon cancers. .
- Natasja L. de Vries
- , Joris van de Haar
- & Emile E. Voest
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Dendritic cells direct circadian anti-tumour immune responses
Rhythmic trafficking of dendritic cells to the tumour draining lymph node governs a circadian response of tumour-antigen-specific CD8+ T cells that is dependent on the circadian expression of the co-stimulatory molecule CD80.
- Chen Wang
- , Coline Barnoud
- & Christoph Scheiermann
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Ferroptosis of tumour neutrophils causes immune suppression in cancer
Pathologically activated neutrophils, termed myeloid-derived suppressor cells, in the tumour microenvironment spontaneously undergo ferroptosis, which negatively regulates anti-tumour immunity through the release of oxygenated lipids, therefore limiting the activity of human and mouse T cells.
- Rina Kim
- , Ayumi Hashimoto
- & Dmitry I. Gabrilovich
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T cells specific for α-myosin drive immunotherapy-related myocarditis
Cytotoxic CD8+ T cells specific for α-myosin are identified as pivotal players in myocarditis associated with immune checkpoint inhibitor anticancer therapies.
- Margaret L. Axelrod
- , Wouter C. Meijers
- & Justin M. Balko
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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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Nociceptor neurons affect cancer immunosurveillance
Melanoma cells interact with pain-mediating sensory neurons by increasing their release of the neuropeptide CGRP, which increases the exhaustion of CD8+ T cells and thus promotes the survival of cancer cells.
- Mohammad Balood
- , Maryam Ahmadi
- & Sebastien Talbot
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STING-induced regulatory B cells compromise NK function in cancer immunity
Systemic treatment of pancreatic cancer with STING agonist stimulates regulatory B cells to express immunosuppressive cytokine IL-35, which weakens the anti-tumour function of natural killer cells.
- Sirui Li
- , Bhalchandra Mirlekar
- & Jenny P.-Y. Ting
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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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PD-1-cis IL-2R agonism yields better effectors from stem-like CD8+ T cells
Binding of the PD1-IL2v immunocytokine to PD-1 and IL-2Rβγ on the same cell leads to an alternative differentiation of stem-like CD8+ T cells into better effectors rather than exhausted T cells in models of both chronic infection and cancer.
- Laura Codarri Deak
- , Valeria Nicolini
- & Pablo Umaña
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Deciphering the immunopeptidome in vivo reveals new tumour antigens
A newly developed genetically engineered mouse model enables the analysis of specific antigen presentation in vivo, providing insights into the tumour immunopeptidome and cancer progression.
- Alex M. Jaeger
- , Lauren E. Stopfer
- & Tyler Jacks
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Neoantigen quality predicts immunoediting in survivors of pancreatic cancer
The human immune system naturally edits cancers of high-quality neoantigens.
- Marta Łuksza
- , Zachary M. Sethna
- & Vinod P. Balachandran
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Extricating human tumour immune alterations from tissue inflammation
Complementary single-cell approaches show that a population of regulatory T cells co-expressing ICOS and IL-1 receptor type 1 is highly enriched in tumours but not in site-matched inflamed non-malignant tissue.
- Florian Mair
- , Jami R. Erickson
- & Martin Prlic
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Fundamental immune–oncogenicity trade-offs define driver mutation fitness
A mathematical framework to estimate the fitness of cancer driver mutations by integrating mutational bias, oncogenicity and immunogenicity finds fundamental trade-offs in cancer evolution.
- David Hoyos
- , Roberta Zappasodi
- & Benjamin D. Greenbaum
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Landscape of helper and regulatory antitumour CD4+ T cells in melanoma
A survey of the CD4+ T cells in human melanomas indicates that immune evasion is mediated through direct stimulation of neoantigen-specific tumour-reactive regulatory T cells by HLA class II-positive melanoma cells.
- Giacomo Oliveira
- , Kari Stromhaug
- & Catherine J. Wu
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Programme of self-reactive innate-like T cell-mediated cancer immunity
A survey of T cell populations in human and mouse tumours identifies a population of cancer-sensing IL-15-activated αβ T cell receptor-positive FCER1G-expressing innate-like T cells with high cytotoxic potential.
- Chun Chou
- , Xian Zhang
- & Ming O. Li
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CAR T cell killing requires the IFNγR pathway in solid but not liquid tumours
A genome-wide CRISPR knockout screen in a model of glioblastoma shows that killing by chimeric antigen receptor T cells requires interferon-γ receptor-dependent adhesion to tumour cells, but cytotoxicity of liquid tumours does not rely on this pathway.
- Rebecca C. Larson
- , Michael C. Kann
- & Marcela V. Maus
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A genome-scale screen for synthetic drivers of T cell proliferation
A genome-scale gain-of-function screen using overexpression of nearly 12,000 open reading frames (ORFs) identifies positive regulators of human T cell function and suggests that ORF-based screens could be applied clinically to improve T cell therapies.
- Mateusz Legut
- , Zoran Gajic
- & Neville E. Sanjana
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Tryptophan depletion results in tryptophan-to-phenylalanine substitutants
Tryptophan depletion, which occurs in tumours, results in in-frame translation across tryptophan-encoding codons by phenylalanine substitution.
- Abhijeet Pataskar
- , Julien Champagne
- & Reuven Agami
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B cell-derived GABA elicits IL-10+ macrophages to limit anti-tumour immunity
A paper in Nature demonstrates that B cell-derived GABA promotes monocyte differentiation into anti-inflammatory macrophages able to limit anti-tumour T cell cytotoxicity.
- Baihao Zhang
- , Alexis Vogelzang
- & Sidonia Fagarasan
PGE2 inhibits TIL expansion by disrupting IL-2 signalling and mitochondrial function