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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Outcomes of Observation vs Stereotactic Ablative Radiation for Oligometastatic Prostate Cancer

JAMA Oncology, Journal Year: 2020, Volume and Issue: 6(5), P. 650 - 650

Published: March 26, 2020

Complete metastatic ablation of oligometastatic prostate cancer may provide an alternative to early initiation androgen deprivation therapy (ADT).To determine if stereotactic ablative radiotherapy (SABR) improves oncologic outcomes in men with cancer.The Observation vs Stereotactic Ablative Radiation for Oligometastatic Prostate Cancer (ORIOLE) phase 2 randomized study accrued participants from 3 US radiation treatment facilities affiliated a university hospital May 2016 March 2018 data cutoff date 20, 2019, analysis. Of 80 screened, 54 recurrent hormone-sensitive and 1 metastases detectable by conventional imaging who had not received ADT within 6 months enrollment or more years total were randomized.Patients 2:1 ratio receive SABR observation.The primary outcome was progression at prostate-specific antigen level increase, detected imaging, symptomatic progression, any reason, death. Predefined secondary toxic effects SABR, local control progression-free survival, Brief Pain Inventory (Short Form)-measured quality life, concordance between membrane (PSMA)-targeted positron emission tomography the identification disease.In randomized, median (range) age 68 (61-70) patients allocated (64-76) those observation. Progression occurred 7 36 (19%) receiving 11 18 (61%) undergoing observation (P = .005). Treatment improved survival (not reached 5.8 months; hazard ratio, 0.30; 95% CI, 0.11-0.81; P .002). Total consolidation PSMA radiotracer-avid disease decreased risk new lesions (16% 63%; .006). No grade greater observed. T-cell receptor sequencing identified significant increased clonotypic expansion following correlation baseline clonality only (0.082085 0.026051; .03).Treatment enhanced PSMA-targeted tomography. induced systemic immune response, phenotype tumor mutation status predict benefit SABR. These results underline importance prospective investigation state integrated biological correlates.ClinicalTrials.gov Identifier: NCT02680587.

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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Detection of immunogenic cell death and its relevance for cancer therapy

Cell Death and Disease, Journal Year: 2020, Volume and Issue: 11(11)

Published: Nov. 26, 2020

Abstract Chemotherapy, radiation therapy, as well targeted anticancer agents can induce clinically relevant tumor-targeting immune responses, which critically rely on the antigenicity of malignant cells and their capacity to generate adjuvant signals. In particular, immunogenic cell death (ICD) is accompanied by exposure release numerous damage-associated molecular patterns (DAMPs), altogether confer a robust adjuvanticity dying cancer cells, they favor recruitment activation antigen-presenting cells. ICD-associated DAMPs include surface-exposed calreticulin (CALR) secreted ATP, annexin A1 (ANXA1), type I interferon, high-mobility group box 1 (HMGB1). Additional hallmarks ICD encompass phosphorylation eukaryotic translation initiation factor 2 subunit-α (EIF2S1, better known eIF2α), autophagy, global arrest in transcription translation. Here, we outline methodological approaches for measuring markers vitro ex vivo discovery next-generation antineoplastic agents, development personalized regimens, identification optimal therapeutic combinations clinical management cancer.

Language: Английский

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Enhancing cancer immunotherapy with nanomedicine

Nature reviews. Immunology, Journal Year: 2020, Volume and Issue: 20(5), P. 321 - 334

Published: Jan. 31, 2020

Language: Английский

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Liver metastasis restrains immunotherapy efficacy via macrophage-mediated T cell elimination

Nature Medicine, Journal Year: 2021, Volume and Issue: 27(1), P. 152 - 164

Published: Jan. 1, 2021

Language: Английский

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Inflammatory microenvironment remodelling by tumour cells after radiotherapy

Nature reviews. Cancer, Journal Year: 2020, Volume and Issue: 20(4), P. 203 - 217

Published: March 11, 2020

Language: Английский

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Immunotherapy in Non–Small Cell Lung Cancer: Facts and Hopes

Clinical Cancer Research, Journal Year: 2019, Volume and Issue: 25(15), P. 4592 - 4602

Published: March 1, 2019

Abstract Immune-checkpoint inhibitors (ICI), particularly of the PD-1 axis, have altered management non–small cell lung cancer (NSCLC) over last 10 years. First demonstrated to improve outcomes in second-line or later therapy advanced disease, ICIs were shown overall survival compared with chemotherapy first-line for patients whose tumors express PD-L1 on at least 50% cells. More recently, combining has been both squamous and nonsquamous NSCLC, regardless expression. However, and, more tumor mutational burden not proven be straightforward indicative biomarkers. We describe advances date utilizing these biomarkers, as well novel markers inflammation, ascertain which are most likely benefit from ICIs. Ongoing translational work promises proportion who agents.

Language: Английский

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Neoantigens: promising targets for cancer therapy

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: Jan. 6, 2023

Abstract Recent advances in neoantigen research have accelerated the development and regulatory approval of tumor immunotherapies, including cancer vaccines, adoptive cell therapy antibody-based therapies, especially for solid tumors. Neoantigens are newly formed antigens generated by cells as a result various tumor-specific alterations, such genomic mutation, dysregulated RNA splicing, disordered post-translational modification, integrated viral open reading frames. recognized non-self trigger an immune response that is not subject to central peripheral tolerance. The quick identification prediction neoantigens been made possible advanced next-generation sequencing bioinformatic technologies. Compared tumor-associated antigens, highly immunogenic provide emerging targets personalized serve prospective predictors survival prognosis checkpoint blockade responses. therapies will be aided understanding mechanism underlying neoantigen-induced anti-tumor streamlining process neoantigen-based immunotherapies. This review provides overview on characterization outlines clinical applications immunotherapeutic strategies based neoantigens. We also explore their current status, inherent challenges, translation potential.

Language: Английский

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Pembrolizumab with or without radiotherapy for metastatic non-small-cell lung cancer: a pooled analysis of two randomised trials

The Lancet Respiratory Medicine, Journal Year: 2020, Volume and Issue: 9(5), P. 467 - 475

Published: Oct. 20, 2020

Language: Английский

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