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Article
Editorial Expression of Concern: The threshold pattern of calcineurin-dependent gene expression is altered by loss of the endogenous inhibitor calcipressin
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Article
X-CHIME enables combinatorial, inducible, lineage-specific and sequential knockout of genes in the immune system
Annotation of immunologic gene function in vivo typically requires the generation of knockout mice, which is time consuming and low throughput. We previously developed CHimeric IMmune Editing (CHIME), a CRISPR...
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Article
Open AccessMicrobiota-dependent regulation of costimulatory and coinhibitory pathways via innate immune sensors and implications for immunotherapy
Our bodies are inhabited by trillions of microorganisms. The host immune system constantly interacts with the microbiota in barrier organs, including the intestines. Over decades, numerous studies have shown t...
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Article
B-cell-specific checkpoint molecules that regulate anti-tumour immunity
The role of B cells in anti-tumour immunity is still debated and, accordingly, immunotherapies have focused on targeting T and natural killer cells to inhibit tumour growth1,2. Here, using high-throughput flow cy...
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Publisher Correction: Targeting PD-L2–RGMb overcomes microbiome-related immunotherapy resistance
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Article
Targeting PD-L2–RGMb overcomes microbiome-related immunotherapy resistance
The gut microbiota is a crucial regulator of anti-tumour immunity during immune checkpoint inhibitor therapy. Several bacteria that promote an anti-tumour response to immune checkpoint inhibitors have been ide...
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Article
PD-1 combination therapy with IL-2 modifies CD8+ T cell exhaustion program
Combination therapy with PD-1 blockade and IL-2 is highly effective during chronic lymphocytic choriomeningitis virus infection1. Here we examine the underlying basis for this synergy. We show that PD-1 + IL-2 co...
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Open AccessPD-L2 controls peripherally induced regulatory T cells by maintaining metabolic activity and Foxp3 stability
Regulatory T (Treg) cells are central to limit immune responses to allergens. Here we show that PD-L2 deficiency prevents the induction of tolerance to ovalbumin and control of airway hyperreactivity, in parti...
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Article
Open AccessGata6+ resident peritoneal macrophages promote the growth of liver metastasis
Emerging evidence suggests that resident macrophages within tissues are enablers of tumor growth. However, a second population of resident macrophages surrounds all visceral organs within the cavities and noth...
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Article
PD-L1–PD-1 interactions limit effector regulatory T cell populations at homeostasis and during infection
Phenotypic and transcriptional profiling of regulatory T (Treg) cells at homeostasis reveals that T cell receptor activation promotes Treg cells with an effector phenotype (eTreg) characterized by the production ...
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Article
Repertoire analyses reveal T cell antigen receptor sequence features that influence T cell fate
T cells acquire a regulatory phenotype when their T cell antigen receptors (TCRs) experience an intermediate- to high-affinity interaction with a self-peptide presented via the major histocompatibility complex...
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Article
Not-so-opposite ends of the spectrum: CD8+ T cell dysfunction across chronic infection, cancer and autoimmunity
CD8+ T cells are critical mediators of cytotoxic effector function in infection, cancer and autoimmunity. In cancer and chronic viral infection, CD8+ T cells undergo a progressive loss of cytokine production and ...
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Article
Open AccessPD-1 pathway regulates ILC2 metabolism and PD-1 agonist treatment ameliorates airway hyperreactivity
Allergic asthma is a leading chronic disease associated with airway hyperreactivity (AHR). Type-2 innate lymphoid cells (ILC2s) are a potent source of T-helper 2 (Th2) cytokines that promote AHR and lung infla...
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Article
Interplay of somatic alterations and immune infiltration modulates response to PD-1 blockade in advanced clear cell renal cell carcinoma
PD-1 blockade has transformed the management of advanced clear cell renal cell carcinoma (ccRCC), but the drivers and resistors of the PD-1 response remain incompletely elucidated. Here, we analyzed 592 tumors...
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Article
Prevention of CAR-T-cell dysfunction
The overexpression of the transcription factor c-Jun improves chimeric-antigen-receptor T-cell functionality and enhances the killing of low-antigen-expressing liquid and solid cancers in mice.
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Article
Fibroblastic reticular cells enhance T cell metabolism and survival via epigenetic remodeling
Lymph node fibroblastic reticular cells (FRCs) respond to signals from activated T cells by releasing nitric oxide, which inhibits T cell proliferation and restricts the size of the expanding T cell pool. Whet...
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Author Correction: Subsets of exhausted CD8+ T cells differentially mediate tumor control and respond to checkpoint blockade
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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Article
Defining ‘T cell exhaustion’
‘T cell exhaustion’ is a broad term that has been used to describe the response of T cells to chronic antigen stimulation, first in the setting of chronic viral infection but more recently in response to tumou...
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Article
Follicular regulatory T cells control humoral and allergic immunity by restraining early B cell responses
Follicular regulatory T (TFR) cells have specialized roles in modulating follicular helper T (TFH) cell activation of B cells. However, the precise role of TFR cells in controlling antibody responses to foreign a...
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Article
PTPN2 regulates the generation of exhausted CD8+ T cell subpopulations and restrains tumor immunity
CD8+ T cell exhaustion is a state of dysfunction acquired in chronic viral infection and cancer, characterized by the formation of Slamf6+ progenitor exhausted and Tim-3+ terminally exhausted subpopulations throu...