Chimeric Antigen Receptor Therapy

New England Journal of Medicine, Journal Year: 2018, Volume and Issue: 379(1), P. 64 - 73

Published: July 4, 2018

Interview with Dr. Carl June on chimeric antigen receptor therapy. (09:04)Download This review addresses T-cell engineering and synthetic immunity, a focus producing durable remissions in patients treatment-refractory tumors. Toxic effects of therapies include cytokine release syndrome neurologic dysfunction.

Language: Английский

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Therapeutic T cell engineering

Nature, Journal Year: 2017, Volume and Issue: 545(7655), P. 423 - 431

Published: May 23, 2017

Language: Английский

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Interleukins in cancer: from biology to therapy

Nature reviews. Cancer, Journal Year: 2021, Volume and Issue: 21(8), P. 481 - 499

Published: June 3, 2021

Language: Английский

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Treg cell-based therapies: challenges and perspectives

Nature reviews. Immunology, Journal Year: 2019, Volume and Issue: 20(3), P. 158 - 172

Published: Dec. 6, 2019

Language: Английский

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Helper T cell differentiation

Cellular and Molecular Immunology, Journal Year: 2019, Volume and Issue: 16(7), P. 634 - 643

Published: March 12, 2019

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Innate Lymphoid Cells: Diversity, Plasticity, and Unique Functions in Immunity

Immunity, Journal Year: 2018, Volume and Issue: 48(6), P. 1104 - 1117

Published: June 1, 2018

Language: Английский

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The glutathione peroxidase Gpx4 prevents lipid peroxidation and ferroptosis to sustain Treg cell activation and suppression of antitumor immunity

Cell Reports, Journal Year: 2021, Volume and Issue: 35(11), P. 109235 - 109235

Published: June 1, 2021

T regulatory (Treg) cells are crucial to maintain immune tolerance and repress antitumor immunity, but the mechanisms governing their cellular redox homeostasis remain elusive. We report that glutathione peroxidase 4 (Gpx4) prevents Treg from lipid peroxidation ferroptosis in regulating immunity. Treg-specific deletion of Gpx4 impairs without substantially affecting survival at steady state. Loss results excessive accumulation peroxides upon cell receptor (TCR)/CD28 co-stimulation. Neutralization blockade iron availability rescue Gpx4-deficient cells. Moreover, elevate generation mitochondrial superoxide production interleukin-1β (IL-1β) facilitates helper 17 (T

Language: Английский

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Meta-Analysis of Leukocyte Diversity in Atherosclerotic Mouse Aortas

Circulation Research, Journal Year: 2020, Volume and Issue: 127(3), P. 402 - 426

Published: July 16, 2020

The diverse leukocyte infiltrate in atherosclerotic mouse aortas was recently analyzed 9 single-cell RNA sequencing and 2 mass cytometry studies. In a comprehensive meta-analysis, we confirm 4 known macrophage subsets-resident, inflammatory, interferon-inducible cell, Trem2 (triggering receptor expressed on myeloid cells-2) foamy macrophages-and identify new subset resembling cavity macrophages. We also find that monocytes, neutrophils, dendritic cells, natural killer innate lymphoid cells-2, CD (cluster of differentiation)-8 T cells form prominent separate immune cell populations aortas. Many CD4 express IL (interleukin)-17 the chemokine CXCR (C-X-C receptor)-6. A small number regulatory helper 1 is identified. Immature naive are present both healthy Our meta-analysis overcomes limitations individual studies that, because their experimental approach, over- or underrepresent certain populations. Mass demonstrate surface phenotype provides valuable information beyond transcriptomes. analysis helps resolve some long-standing controversies field. First,

Language: Английский

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Targeting EZH2 Reprograms Intratumoral Regulatory T Cells to Enhance Cancer Immunity

Cell Reports, Journal Year: 2018, Volume and Issue: 23(11), P. 3262 - 3274

Published: June 1, 2018

Regulatory T cells (Tregs) are critical for maintaining immune homeostasis, but their presence in tumor tissues impairs anti-tumor immunity and portends poor prognoses cancer patients. Here, we reveal a mechanism to selectively target reprogram the function of tumor-infiltrating Tregs (TI-Tregs) by exploiting dependency on histone H3K27 methyltransferase enhancer zeste homolog 2 (EZH2) tumors. Disruption EZH2 activity Tregs, either pharmacologically or genetically, drove acquisition pro-inflammatory functions TI-Tregs, remodeling microenvironment enhancing recruitment CD8+ CD4+ effector that eliminate Moreover, abolishing was mechanistically distinct from, more potent than, less toxic than generalized Treg depletion approach. This study reveals strategy mitigates autoimmunity reprogramming tumors enhance anti-cancer immunity.

Language: Английский

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A cellular and molecular view of T helper 17 cell plasticity in autoimmunity

Journal of Autoimmunity, Journal Year: 2017, Volume and Issue: 87, P. 1 - 15

Published: Dec. 22, 2017

Since the original identification of T helper 17 (Th17) subset in 2005, it has become evident that these cells do not only contribute to host defence against pathogens, such as bacteria and fungi, but they are also critically involved pathogenesis many autoimmune diseases. In contrast classic Th1 Th2 cells, which represent rather stably polarized subsets, Th17 display remarkable heterogeneity plasticity. This been attributed characteristics key transcription factor guides differentiation, retinoic acid receptor-related orphan nuclear receptor gamma (RORγ). Unlike ‘master regulators’ T-bet GATA3 orchestrate respectively, RORγ controls at relatively few loci cells. Moreover, its expression is stabilized by positive feedback loops influenced environmental cues, allowing for substantial functional Importantly, a IL-17/IFNγ double-producing was identified both human mouse models. Evidence accumulating pathogenic drivers diseases, including rheumatoid arthritis, multiple sclerosis inflammatory bowel disease. addition, have disorders role autoimmunity remains unclear, sarcoidosis. The observed plasticity towards phenotype can be explained extensive epigenetic priming IFNG locus fact, an chromatin landscape remarkably similar On other hand, capabilities restrained stimulating IL-10 production transdifferentiation into producing regulatory type 1 (Tr1) this review, we discuss recent advances our knowledge on cellular molecular mechanisms We focus transcriptional regulation program, dynamics involved, how genetic variants associated with may affect immune responses through distal gene elements. Finally, implications cell treatment diseases will discussed.

Language: Английский

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