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Autoimmunity in Down’s syndrome via cytokines, CD4 T cells and CD11c+ B cells
An autoimmune-prone state of steady-state cytokinopathy, hyperactivated CD4 T cells and ongoing B cell activation contributes to a breach in immune tolerance in individuals with Down’s syndrome.
- Louise Malle
- , Roosheel S. Patel
- & Dusan Bogunovic
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Reducing affinity as a strategy to boost immunomodulatory antibody agonism
In contrast to direct-targeting monoclonal antibodies, low affinity confers agonistic monoclonal antibodies with more potency.
- Xiaojie Yu
- , Christian M. Orr
- & Mark S. Cragg
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Article
| Open Access
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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Decade-long leukaemia remissions with persistence of CD4+ CAR T cells
Infusion of CD19-directed chimeric antigen receptor T cells into two patients with chronic lymphocytic leukaemia resulted in complete tumour remission and persistence of the infused cells more than ten years later.
- J. Joseph Melenhorst
- , Gregory M. Chen
- & Carl H. June
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Senolytic CAR T cells reverse senescence-associated pathologies
Chimeric antigen receptor (CAR) T cells targeting uPAR, a cell-surface protein that is upregulated on senescent cells, eliminate senescent cells in vitro and in vivo and reduce liver fibrosis in mice.
- Corina Amor
- , Judith Feucht
- & Scott W. Lowe
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Article |
Sialylation of immunoglobulin E is a determinant of allergic pathogenicity
A specific type of glycosylation—sialylation—is more common on immunoglobulin E from individuals with a peanut allergys than from non-atopic people, suggesting that it has a role in regulating anaphylaxis.
- Kai-Ting C. Shade
- , Michelle E. Conroy
- & Robert M. Anthony
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c-Jun overexpression in CAR T cells induces exhaustion resistance
Chimeric antigen receptor (CAR) T cells engineered to overexpress the canonical AP-1 transcription factor c-Jun are resistant to T cell exhaustion, and provide enhanced therapeutic benefit in mouse tumour models.
- Rachel C. Lynn
- , Evan W. Weber
- & Crystal L. Mackall
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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 |
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 |
TGFβ attenuates tumour response to PD-L1 blockade by contributing to exclusion of T cells
In humans, TGFβ signalling is associated with lack of response to immunotherapy in immune-excluded tumours; in mouse models of this immune phenotype, robust tumour infiltration by T cells and tumour regression are observed only when checkpoint inhibition is combined with inhibition of TGFβ signalling.
- Sanjeev Mariathasan
- , Shannon J. Turley
- & Thomas Powles
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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 |
Metabolic control of TH17 and induced Treg cell balance by an epigenetic mechanism
Metabolic changes in T cells can affect the genomic methylation status of key transcription factors and regulate the fate decision between induced regulatory T cells and T helper 17 cells.
- Tao Xu
- , Kelly M. Stewart
- & Sheng Ding
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Letter |
Targeting a CAR to the TRAC locus with CRISPR/Cas9 enhances tumour rejection
Introducing chimeric antigen receptors into the endogenous T-cell receptor locus reduces tonic signalling, averts accelerated T-cell differentiation and delays T-cell exhaustion, leading to enhanced function and anti-tumour efficacy compared to random integrations.
- Justin Eyquem
- , Jorge Mansilla-Soto
- & Michel Sadelain
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Letter |
Pathologically expanded peripheral T helper cell subset drives B cells in rheumatoid arthritis
The authors identify in patients with rheumatoid arthritis a pathogenic subset of CD4+ T cells that augments B cell responses within inflamed tissues.
- Deepak A. Rao
- , Michael F. Gurish
- & Michael B. Brenner
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Normalizing the environment recapitulates adult human immune traits in laboratory mice
The immune system of laboratory mice raised in an ultra-hygienic environment resembles that ofnewborn humans, but can be induced to resemble the immune system of adult humans or 'dirty' mice by co-housing with pet store-bought mice.
- Lalit K. Beura
- , Sara E. Hamilton
- & David Masopust
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T-cell exhaustion, co-stimulation and clinical outcome in autoimmunity and infection
CD8 T-cell exhaustion, although a negative prognostic indicator during persistent infections, is shown to be associated with a good outcome in autoimmune and inflammatory diseases.
- Eoin F. McKinney
- , James C. Lee
- & Kenneth G. C. Smith
Deconstruction of rheumatoid arthritis synovium defines inflammatory subtypes