Hallmarks of response, resistance, and toxicity to immune checkpoint blockade

Cell, Journal Year: 2021, Volume and Issue: 184(21), P. 5309 - 5337

Published: Oct. 1, 2021

Language: Английский

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Interleukin-6 blockade abrogates immunotherapy toxicity and promotes tumor immunity

Cancer Cell, Journal Year: 2022, Volume and Issue: 40(5), P. 509 - 523.e6

Published: May 1, 2022

Language: Английский

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Fecal microbiota transplantation plus anti-PD-1 immunotherapy in advanced melanoma: a phase I trial

Nature Medicine, Journal Year: 2023, Volume and Issue: 29(8), P. 2121 - 2132

Published: July 6, 2023

Language: Английский

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Understanding and treating the inflammatory adverse events of cancer immunotherapy

Cell, Journal Year: 2021, Volume and Issue: 184(6), P. 1575 - 1588

Published: March 1, 2021

Language: Английский

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Immune-related adverse events of immune checkpoint inhibitors: a review

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: May 25, 2023

Since the first Immune Checkpoint Inhibitor was developed, tumor immunotherapy has entered a new era, and response rate survival of many cancers have also been improved. Despite success immune checkpoint inhibitors, resistance limits number patients who can achieve lasting response, immune-related adverse events complicate treatment. The mechanism (irAEs) is unclear. We summarize discuss mechanisms action different types their possible mechanisms, describe strategies targets for prevention therapeutic interventions to mitigate them.

Language: Английский

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Advancing to the era of cancer immunotherapy

Cancer Communications, Journal Year: 2021, Volume and Issue: 41(9), P. 803 - 829

Published: June 24, 2021

Cancer greatly affects the quality of life humans worldwide and number patients suffering from it is continuously increasing. Over last century, numerous treatments have been developed to improve survival cancer but substantial progress still needs be made before can truly cured. In recent years, antitumor immunity has become most debated topic in research booming development immunotherapy led a new epoch therapy. this review, we describe relationships between tumors immune system, rise immunotherapy. Then, summarize characteristics tumor-associated immunotherapeutic strategies with various molecular mechanisms by showing typical molecules whose antibodies are broadly used clinic those that under investigation. We also discuss important elements individual cells whole human body, including cellular mutations modulation, metabolic reprogramming, microbiome, contexture. addition, present observations technical advancements both diagnostic therapeutic methods aimed at Lastly, controversies challenges negatively impact patient outcomes.

Language: Английский

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Second Near‐Infrared Light‐Activatable Polymeric Nanoantagonist for Photothermal Immunometabolic Cancer Therapy

Advanced Materials, Journal Year: 2021, Volume and Issue: 33(36)

Published: July 23, 2021

Immunometabolic modulation offers new opportunities to treat cancers as it is highly associated with cancer progression and immunosuppressive microenvironment. However, traditional regimens using nonselective small-molecule immunomodulators lead the off-target adverse effects insufficient therapeutic outcomes. Herein a second near-infrared (NIR-II) photothermally activatable semiconducting polymeric nanoantagonist (ASPA) for synergistic photothermal immunometabolic therapy of reported. ASPA backbone obtained by conjugating vipadenant, an antagonist adenosine A2A receptor, onto NIR-II light-absorbing polymer via azo-based thermolabile linker. Under deep-penetrating photoirradiation, induces tumor thermal ablation subsequently immunogenic cell death, triggers cleavage linker, releases block adenosinergic pathway. Such remotely controlled regulation potentiates cytotoxic T functions while suppresses regulatory activities, leading efficient primary inhibition, pulmonary metastasis prevention, long-term immunological memory. Thereby, this work provides generic approach precise spatiotemporal immunometabolism.

Language: Английский

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Immune mechanisms of toxicity from checkpoint inhibitors

Trends in cancer, Journal Year: 2023, Volume and Issue: 9(7), P. 543 - 553

Published: April 27, 2023

Immunotherapy has changed the treatment landscape for cancer over past decade. Inhibitors of immune checkpoint proteins cytotoxic T lymphocyte antigen (CTLA)-4, programmed death (PD)-1, and PD ligand 1 (PD-L1) can induce durable remissions in a subset patients with metastatic disease. However, these treatments be limited by inflammatory toxicities that affect any organ system body some cases life threatening. Considerable progress been made understanding drivers as well effective management strategies. Further research into molecular cellular mechanisms drive toxicity will enable better prediction development optimized therapies avoid interfering antitumor immunity. In this review, we discuss our current from inhibitors (ICIs) propose optimal strategies toxicities.

Language: Английский

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Association of Radiation Therapy With Risk of Adverse Events in Patients Receiving Immunotherapy

JAMA Oncology, Journal Year: 2022, Volume and Issue: 8(2), P. 232 - 232

Published: Jan. 6, 2022

Importance

Immune checkpoint inhibitors (ICIs) and radiation therapy (RT) are widely used to treat various cancers, but little data available guide clinicians on ICI use sequentially with RT.

Objective

To assess whether there is an increased risk of serious adverse events (AEs) associated RT given within 90 days prior ICI.

Design, Setting, Participants

Individual patient were pooled from 68 prospective trials ICIs submitted in initial or supplemental licensing applications the US Food Drug Administration (FDA) databases through December 2019. Two cohorts generated: (1) patients who received beginning (2) those did not receive therapy, AE frequencies determined. A 1:1 propensity score–matched analysis was performed.

Interventions

All (atezolizumab, avelumab, cemiplimab, durvalumab, ipilimumab, nivolumab, pembrolizumab); 1733 starting 13 956 not.

Main Outcomes Measures

The primary outcome frequency severity AEs. Incidence AEs compared descriptively between participants vs set. Because all analyses exploratory (ie, preplanned no alpha allocated), assessment for statistical significance differences groups considered appropriate.

Results

total 25 469 identified; 8634 excluded because they lacked comparators had (n = 976), 4949), outside target window 2338), missing 1 more variables 371), leaving 16 835 included analysis. majority younger than 65 years (9447 [56.1%]), male (10 459 [62.1%]), White (13 422 [79.7%]). Patients receiving generally similar rates overall average absolute difference across 1.2%, ranged 0% neurologic 8% fatigue. No grade 3 4 observed 2 (absolute 0.01% 2%). These findings persisted after score matching.

Conclusions Relevance

In this analysis, administration following appear be Thus, it would safe administer should confirmed future trials.

Language: Английский

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Harnessing big data to characterize immune-related adverse events

Nature Reviews Clinical Oncology, Journal Year: 2022, Volume and Issue: 19(4), P. 269 - 280

Published: Jan. 17, 2022

Language: Английский

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