Pan-cancer single-cell landscape of tumor-infiltrating T cells

Science, Journal Year: 2021, Volume and Issue: 374(6574)

Published: Dec. 16, 2021

T cells play a central role in cancer immunotherapy, but we lack systematic comparison of the heterogeneity and dynamics tumor-infiltrating across types. We built single-cell RNA-sequencing pan-cancer atlas for 316 donors 21 types revealed distinct cell composition patterns. found multiple state-transition paths exhaustion CD8+ preference those among different tumor Certain populations showed specific correlation with patient properties such as mutation burden, shedding light on possible determinants microenvironment. compositions within tumors alone could classify patients into groups clinical trait specificity, providing new insights immunity precision immunotherapy targeting cells.

Language: Английский

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Developmental Relationships of Four Exhausted CD8+ T Cell Subsets Reveals Underlying Transcriptional and Epigenetic Landscape Control Mechanisms

Immunity, Journal Year: 2020, Volume and Issue: 52(5), P. 825 - 841.e8

Published: May 1, 2020

Language: Английский

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Acquired Resistance to Immune Checkpoint Inhibitors

Cancer Cell, Journal Year: 2020, Volume and Issue: 37(4), P. 443 - 455

Published: April 1, 2020

Language: Английский

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The Next Decade of Immune Checkpoint Therapy

Cancer Discovery, Journal Year: 2021, Volume and Issue: 11(4), P. 838 - 857

Published: April 1, 2021

Immune checkpoint therapy (ICT) can provide durable clinical responses and improve overall survival. However, only subsets of patients with specific tumor types respond to ICT. Thus, significant challenges remain, including understanding pathways resistance, optimizing patient selection, improving management immune-related adverse events, identifying rational therapeutic combinations. These will need a focused approach encompassing both basic research, the integration reverse translational studies. This integrated lead identification potential targets for subsequent trials, which guide decisions as we develop novel combination strategies maximize efficacy minimize toxicities patients. SIGNIFICANCE: ICTs induce antitumor cancer. Recent evidence suggests that combinatorial response by overcoming primary adaptive resistance mechanisms, although these may carry an increased risk immune-mediated toxicities. review surveys current mechanisms active areas investigation, proposes path forward minimizing through better selection

Language: Английский

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Targeting the epigenetic regulation of antitumour immunity

Nature Reviews Drug Discovery, Journal Year: 2020, Volume and Issue: 19(11), P. 776 - 800

Published: Sept. 14, 2020

Language: Английский

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Transient rest restores functionality in exhausted CAR-T cells through epigenetic remodeling

Science, Journal Year: 2021, Volume and Issue: 372(6537)

Published: April 1, 2021

CAR-T cells rest to get back in the race Chimeric antigen receptor (CAR)–T cells, which are engineered target specific tumor antigens, increasingly used as an immunotherapy. have shown promising results patients, particularly hematologic cancers, but their anticancer activity can be limited by onset of exhaustion and loss effectiveness. Weber et al. characterized phenotypic epigenomic changes associated with cell caused continuous beneficial effects transient periods (see Perspective Mamonkin Brenner). The authors tested different approaches for providing these periods, such using drug dasatinib temporarily suppress T activity, helped prevent improved antitumor mouse models. Science , this issue p. eaba1786 ; see also 34

Language: Английский

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Galectin-9 interacts with PD-1 and TIM-3 to regulate T cell death and is a target for cancer immunotherapy

Nature Communications, Journal Year: 2021, Volume and Issue: 12(1)

Published: Feb. 5, 2021

The two T cell inhibitory receptors PD-1 and TIM-3 are co-expressed during exhausted differentiation, recent evidence suggests that their crosstalk regulates exhaustion immunotherapy efficacy; however, the molecular mechanism is unclear. Here we show contributes to persistence of

Language: Английский

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Comprehensive Profiling of an Aging Immune System Reveals Clonal GZMK+ CD8+ T Cells as Conserved Hallmark of Inflammaging

Immunity, Journal Year: 2020, Volume and Issue: 54(1), P. 99 - 115.e12

Published: Dec. 2, 2020

Language: Английский

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Disturbed mitochondrial dynamics in CD8+ TILs reinforce T cell exhaustion

Nature Immunology, Journal Year: 2020, Volume and Issue: 21(12), P. 1540 - 1551

Published: Oct. 5, 2020

Language: Английский

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Metabolic barriers to cancer immunotherapy

Nature reviews. Immunology, Journal Year: 2021, Volume and Issue: 21(12), P. 785 - 797

Published: April 29, 2021

Language: Английский

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