Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018

Cell Death and Differentiation, Journal Year: 2018, Volume and Issue: 25(3), P. 486 - 541

Published: Jan. 23, 2018

Over the past decade, Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for definition and interpretation of cell death from morphological, biochemical, functional perspectives. Since field continues to expand novel mechanisms that orchestrate multiple pathways are unveiled, we propose an updated classification subroutines focusing mechanistic essential (as opposed correlative dispensable) aspects process. As provide molecularly oriented definitions terms including intrinsic apoptosis, extrinsic mitochondrial permeability transition (MPT)-driven necrosis, necroptosis, ferroptosis, pyroptosis, parthanatos, entotic death, NETotic lysosome-dependent autophagy-dependent immunogenic cellular senescence, mitotic catastrophe, discuss utility neologisms refer highly specialized instances these processes. The mission NCCD is a widely accepted nomenclature in support continued development field.

Language: Английский

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Dendritic cells in cancer immunology and immunotherapy

Nature reviews. Immunology, Journal Year: 2019, Volume and Issue: 20(1), P. 7 - 24

Published: Aug. 29, 2019

Language: Английский

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The immune contexture and Immunoscore in cancer prognosis and therapeutic efficacy

Nature reviews. Cancer, Journal Year: 2020, Volume and Issue: 20(11), P. 662 - 680

Published: Aug. 4, 2020

Language: Английский

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Mitochondrial metabolism and cancer

Cell Research, Journal Year: 2017, Volume and Issue: 28(3), P. 265 - 280

Published: Dec. 8, 2017

Glycolysis has long been considered as the major metabolic process for energy production and anabolic growth in cancer cells. Although such a view instrumental development of powerful imaging tools that are still used clinics, it is now clear mitochondria play key role oncogenesis. Besides exerting central bioenergetic functions, provide indeed building blocks tumor anabolism, control redox calcium homeostasis, participate transcriptional regulation, govern cell death. Thus, constitute promising targets novel anticancer agents. However, tumors arise, progress, respond to therapy context an intimate crosstalk with host immune system, many immunological functions rely on intact mitochondrial metabolism. Here, we review cell-intrinsic cell-extrinsic mechanisms through which influence all steps oncogenesis, focus therapeutic potential targeting metabolism therapy.

Language: Английский

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Using immunotherapy to boost the abscopal effect

Nature reviews. Cancer, Journal Year: 2018, Volume and Issue: 18(5), P. 313 - 322

Published: Feb. 16, 2018

Language: Английский

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Immunostimulation with chemotherapy in the era of immune checkpoint inhibitors

Nature Reviews Clinical Oncology, Journal Year: 2020, Volume and Issue: 17(12), P. 725 - 741

Published: Aug. 5, 2020

Language: Английский

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Consensus guidelines for the definition, detection and interpretation of immunogenic cell death

Journal for ImmunoTherapy of Cancer, Journal Year: 2020, Volume and Issue: 8(1), P. e000337 - e000337

Published: March 1, 2020

Cells succumbing to stress via regulated cell death (RCD) can initiate an adaptive immune response associated with immunological memory, provided they display sufficient antigenicity and adjuvanticity. Moreover, multiple intracellular microenvironmental features determine the propensity of RCD drive immunity. Here, we provide updated operational definition immunogenic (ICD), discuss key factors that dictate ability dying cells response, summarize experimental assays are currently available for assessment ICD in vitro vivo, formulate guidelines their interpretation.

Language: Английский

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Immunogenic cell stress and death

Nature Immunology, Journal Year: 2022, Volume and Issue: 23(4), P. 487 - 500

Published: Feb. 10, 2022

Language: Английский

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Radiotherapy and Immunotherapy Promote Tumoral Lipid Oxidation and Ferroptosis via Synergistic Repression of SLC7A11

Cancer Discovery, Journal Year: 2019, Volume and Issue: 9(12), P. 1673 - 1685

Published: Sept. 25, 2019

Abstract A challenge in oncology is to rationally and effectively integrate immunotherapy with traditional modalities, including radiotherapy. Here, we demonstrate that radiotherapy induces tumor-cell ferroptosis. Ferroptosis agonists augment ferroptosis antagonists limit efficacy tumor models. Immunotherapy sensitizes tumors by promoting Mechanistically, IFNγ derived from immunotherapy-activated CD8+ T cells radiotherapy-activated ATM independently, yet synergistically, suppresses SLC7A11, a unit of the glutamate–cystine antiporter xc−, resulting reduced cystine uptake, enhanced lipid oxidation ferroptosis, improved control. Thus, an unappreciated mechanism focus for development effective combinatorial cancer therapy. Significance: This article describes as previously action Further, it shows novel point synergy between Finally, nominates critical regulator mechanistic determinant immunotherapy. highlighted In Issue feature, p. 1631

Language: Английский

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Effect of Pembrolizumab After Stereotactic Body Radiotherapy vs Pembrolizumab Alone on Tumor Response in Patients With Advanced Non–Small Cell Lung Cancer

JAMA Oncology, Journal Year: 2019, Volume and Issue: 5(9), P. 1276 - 1276

Published: July 11, 2019

Importance

Many patients with advanced non–small cell lung cancer (NSCLC) receiving immunotherapy show primary resistance. High-dose radiotherapy can lead to increased tumor antigen release, improved presentation, and T-cell infiltration. This may enhance the effects of checkpoint inhibition.

Objective

To assess whether stereotactic body on a single site preceding pembrolizumab treatment enhances response in metastatic NSCLC.

Design, Setting, Participants

Multicenter, randomized phase 2 study (PEMBRO-RT) 92 NSCLC enrolled between July 1, 2015, March 31, 2018, regardless programmed death–ligand 1 (PD-L1) status. Data analysis was intention-to-treat population.

Interventions

Pembrolizumab (200 mg/kg every 3 weeks) either alone (control arm) or after (3 doses 8 Gy) (experimental until confirmed radiographic progression, unacceptable toxic effects, investigator decision, patient withdrawal consent, maximum 24 months.

Main Outcomes Measures

Improvement overall rate (ORR) at 12 weeks from 20% control arm 50% experimental withP < .10.

Results

Of enrolled, 76 were (n = 40) 36). those, median age 62 years (range, 35-78 years), 44 (58%) men. The ORR 18% vs 36% (P .07). Median progression-free survival 1.9 months (95% CI, 1.7-6.9 months) 6.6 4.0-14.6 (hazard ratio, 0.71; 95% 0.42-1.18;P .19), 7.6 6.0-13.9 15.9 7.1 not reached) 0.66; 0.37-1.18;P .16). Subgroup analyses showed largest benefit addition PD-L1–negative tumors. No increase treatment-related observed arm.

Conclusions Relevance

Stereotactic prior well tolerated. Although doubling observed, results did meet study's prespecified end point criteria for meaningful clinical benefit. Positive largely influenced by subgroup, which had significantly survival. These suggest that larger trial is necessary determine activate noninflamed toward more inflamed microenvironment.

Trial Registration

ClinicalTrials.gov identifier:NCT02492568

Language: Английский

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