Monocyte-derived IL-1 and IL-6 are differentially required for cytokine-release syndrome and neurotoxicity due to CAR T cells

Nature Medicine, Journal Year: 2018, Volume and Issue: 24(6), P. 739 - 748

Published: May 24, 2018

Language: Английский

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From chemotherapy to biological therapy: A review of novel concepts to reduce the side effects of systemic cancer treatment (Review)

International Journal of Oncology, Journal Year: 2018, Volume and Issue: 54(2), P. 407 - 419

Published: Dec. 10, 2018

The side effects of systemic chemotherapy used to treat cancer are often severe. For decades, oncologists have focused on treating the tumor, which may result in damage tumor‑bearing host and its immune system. Recently, much attention has been paid system patients activation via biological therapies. Biological therapies, including immunotherapy oncolytic virus (OV) therapy, more physiological well tolerated. present review elucidated how these therapies work why be better tolerated: i) In contrast chemotherapy, immunotherapies induce a memory function adaptive immunity system; ii) aim specifically activate against cancer; low due tolerance mechanisms, maintain integrity body presence B T lymphocytes with their antigen‑receptor specificities and; iii) type I interferon response, is evoked by OVs, an ancient innate defense support system, therefore benefit treatment. immunotherapy, reducing increasing long‑lasting efficacy therapy.

Language: Английский

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Immunosenescence and Inflamm-Aging As Two Sides of the Same Coin: Friends or Foes?

Frontiers in Immunology, Journal Year: 2018, Volume and Issue: 8

Published: Jan. 9, 2018

The immune system is the most important protective physiological of organism. It has many connections with other systems and is, in fact, often considered as part larger neuro-endocrine-immune axis. Most experimental data on changes aging show a decline parameters when compared to young healthy subjects. bulk these termed immunosenescence. Immunosenescence been for some time detrimental because it leads subclinical accumulation proinflammatory factors inflamm-aging. Together, immunosenescence inflamm-aging are suggested stand at origin diseases elderly, such infections, cancer, autoimmune disorders, chronic inflammatory diseases. However, an increasing number immune-gerontologists have challenged this negative interpretation respect its significance aging-related alterations system. If one considers from evolutionary perspective, they can be viewed preferably adaptive or remodeling rather than solely detrimental. Whereas conceivable that global may lead various diseases, also obvious needed extended survival/longevity. Recent cumulative suggest that, without existence immunosenescence/inflamm-aging duo (representing two sides same phenomenon), human longevity would greatly shortened. This review summarizes recent dynamic reassessment aging. Accordingly, attempts intervene by targeting rejuvenation, more suitable aim maintain general homeostasis function appropriately improving immune-inflammatory-functions.

Language: Английский

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CAR T Cells for Solid Tumors: New Strategies for Finding, Infiltrating, and Surviving in the Tumor Microenvironment

Frontiers in Immunology, Journal Year: 2019, Volume and Issue: 10

Published: Feb. 4, 2019

Chimeric antigen receptor (CAR) T cells, cells that have been genetically engineered to express a recognizes specific antigen, given rise breakthroughs in treating hematological malignancies. However, their success solid tumors has limited. The unique challenges posed CAR cell therapy by can be described three steps: finding, entering, and surviving the tumor. use of dual designs recognize multiple antigens at once local administration are both strategies used overcome hurdle localization Additionally, immunosuppressive tumor microenvironment implications for function terms differentiation exhaustion, combining CARs with checkpoint blockade or depletion other suppressive factors shown very promising results mitigate phenomenon exhaustion. Finally, identifying overcoming mechanisms associated dysfunction is vital importance generating proliferate successfully eliminate cells. structure costimulatory domains chosen may play an important role overall TME, "armored" secrete cytokines third- fourth-generation offer ways enhance function.

Language: Английский

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B cell maturation antigen–specific CAR T cells are clinically active in multiple myeloma

Journal of Clinical Investigation, Journal Year: 2019, Volume and Issue: 129(6), P. 2210 - 2221

Published: March 21, 2019

BACKGROUND. CAR T cells are a promising therapy for hematologic malignancies. B cell maturation antigen (BCMA) is rational target in multiple myeloma (MM).

Language: Английский

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Tumor-infiltrating lymphocytes in the immunotherapy era

Cellular and Molecular Immunology, Journal Year: 2020, Volume and Issue: 18(4), P. 842 - 859

Published: Nov. 2, 2020

Language: Английский

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Single-cell RNA-seq reveals TOX as a key regulator of CD8+ T cell persistence in chronic infection

Nature Immunology, Journal Year: 2019, Volume and Issue: 20(7), P. 890 - 901

Published: June 17, 2019

Language: Английский

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Personal neoantigen vaccines induce persistent memory T cell responses and epitope spreading in patients with melanoma

Nature Medicine, Journal Year: 2021, Volume and Issue: 27(3), P. 515 - 525

Published: Jan. 21, 2021

Language: Английский

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Discriminating mild from critical COVID-19 by innate and adaptive immune single-cell profiling of bronchoalveolar lavages

Cell Research, Journal Year: 2021, Volume and Issue: 31(3), P. 272 - 290

Published: Jan. 21, 2021

Abstract How the innate and adaptive host immune system miscommunicate to worsen COVID-19 immunopathology has not been fully elucidated. Here, we perform single-cell deep-immune profiling of bronchoalveolar lavage (BAL) samples from 5 patients with mild 26 critical in comparison BALs non-COVID-19 pneumonia normal lung. We use pseudotime inference build T-cell monocyte-to-macrophage trajectories model gene expression changes along them. In COVID-19, CD8 + resident-memory (T RM ) CD4 T-helper-17 H17 cells undergo active (presumably antigen-driven) expansion towards end trajectory, are characterized by good effector functions, while they remain more naïve. Vice versa, T-cells T-helper-1 characteristics H1 -like) expressing exhaustion markers EX enriched halfway their where also exhibit show evidence inflammation-associated stress at trajectories. Monocyte-to-macrophage that chronic hyperinflammatory monocytes alveolar macrophages, otherwise anti-inflammatory antigen-presenting characteristics, depleted. contribute an ATP-purinergic signaling-inflammasome footprint could enable associated fibrosis disease-severity. Finally, viral RNA-tracking reveals infected lung epithelial cells, a significant proportion neutrophils macrophages involved clearance.

Language: Английский

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The integration of inflammaging in age-related diseases

Seminars in Immunology, Journal Year: 2018, Volume and Issue: 40, P. 17 - 35

Published: Oct. 2, 2018

Language: Английский

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