• Login
    View Item 
    •   Home
    • The Christie Research Publications Repository
    • All Christie Publications
    • View Item
    •   Home
    • The Christie Research Publications Repository
    • All Christie Publications
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Browse

    All of ChristieCommunitiesTitleAuthorsIssue DateSubmit DateSubjectsThis CollectionTitleAuthorsIssue DateSubmit DateSubjects

    My Account

    LoginRegister

    Local Links

    The Christie WebsiteChristie Library and Knowledge Service

    Statistics

    Display statistics

    Checkpoint-blocker-induced autoimmunity is associated with favourable outcome in metastatic melanoma and distinct T-cell expression profiles

    • CSV
    • RefMan
    • EndNote
    • BibTex
    • RefWorks
    Thumbnail
    Name:
    33723392.pdf
    Size:
    971.3Kb
    Format:
    PDF
    Description:
    From UNPAYWALL
    Download
    Authors
    Ye, W.
    Olsson-Brown, A.
    Watson, R. A.
    Cheung, V. T. F.
    Morgan, Robert David
    Nassiri, I.
    Cooper, R.
    Taylor, C. A.
    Akbani, U.
    Brain, O.
    Matin, R. N.
    Coupe, N.
    Middleton, M. R.
    Coles, M.
    Sacco, J. J.
    Payne, M. J.
    Fairfax, B. P.
    Show allShow less
    Affiliation
    Oxford University Clinical Academic Graduate School, University of Oxford, Oxford
    Issue Date
    2021
    
    Metadata
    Show full item record
    Abstract
    Background: Immune checkpoint blockers (ICBs) activate CD8+ T cells, eliciting both anti-cancer activity and immune-related adverse events (irAEs). The relationship of irAEs with baseline parameters and clinical outcome is unclear. Methods: Retrospective evaluation of irAEs on survival was performed across primary (N = 144) and secondary (N = 211) independent cohorts of patients with metastatic melanoma receiving single agent (pembrolizumab/nivolumab-sICB) or combination (nivolumab and ipilimumab-cICB) checkpoint blockade. RNA from pre-treatment and post-treatment CD8+ T cells was sequenced and differential gene expression according to irAE development assessed. Results: 58.3% of patients developed early irAEs and this was associated with longer progression-free (PFS) and overall survival (OS) across both cohorts (log-rank test, OS: P < 0.0001). Median survival for patients without irAEs was 16.6 months (95% CI: 10.9-33.4) versus not-reached (P = 2.8 × 10-6). Pre-treatment monocyte and neutrophil counts, but not BMI, were additional predictors of clinical outcome. Differential expression of numerous gene pathway members was observed in CD8+ T cells according to irAE development, and patients not developing irAEs demonstrating upregulated CXCR1 pre- and post-treatment. Conclusions: Early irAE development post-ICB is associated with favourable survival in MM. Development of irAEs is coupled to expression of numerous gene pathways, suggesting irAE development in-part reflects baseline immune activation.
    Citation
    Ye W, Olsson-Brown A, Watson RA, Cheung VTF, Morgan RD, Nassiri I, et al. Checkpoint-blocker-induced autoimmunity is associated with favourable outcome in metastatic melanoma and distinct T-cell expression profiles. Br J Cancer. 2021.
    Journal
    British Journal of Cancer
    URI
    http://hdl.handle.net/10541/623969
    DOI
    10.1038/s41416-021-01310-3
    PubMed ID
    33723392
    Additional Links
    https://dx.doi.org/10.1038/s41416-021-01310-3
    Type
    Article
    Language
    en
    ae974a485f413a2113503eed53cd6c53
    10.1038/s41416-021-01310-3
    Scopus Count
    Collections
    All Christie Publications

    entitlement

    Related articles

    • Combination anti-PD1 and ipilimumab therapy in patients with advanced melanoma and pre-existing autoimmune disorders.
    • Authors: Brown LJ, Weppler A, Bhave P, Allayous C, Patrinely JR Jr, Ott P, Sandhu S, Haydon A, Lebbe C, Johnson DB, Long GV, Menzies AA, Carlino MS
    • Issue date: 2021 May
    • Systematic review and meta-analysis efficacy and safety of immune checkpoint inhibitors in advanced melanoma patients with anti-PD-1 progression: a systematic review and meta-analysis.
    • Authors: Alrabadi NN, Abushukair HM, Ababneh OE, Syaj SS, Al-Horani SS, Qarqash AA, Darabseh OA, Al-Sous MM, Al-Aomar SR, Ahmed YB, Haddad R, Al Qarqaz FA
    • Issue date: 2021 Sep
    • The association between immune-related adverse events and survival outcomes in Asian patients with advanced melanoma receiving anti-PD-1 antibodies.
    • Authors: Wu CE, Yang CK, Peng MT, Huang PW, Chang CF, Yeh KY, Chen CB, Wang CL, Hsu CW, Chen IW, Lin CT, Ueng SH, Lin G, Lin YF, Cheng CY, Chang JW
    • Issue date: 2020 Oct 21
    • Immune adverse events (irAEs) with adjuvant ipilimumab in melanoma, use of immunosuppressants and association with outcome: ECOG-ACRIN E1609 study analysis.
    • Authors: Tarhini AA, Kang N, Lee SJ, Hodi FS, Cohen GI, Hamid O, Hutchins LF, Sosman JA, Kluger HM, Eroglu Z, Koon HB, Lawrence DP, Kendra KL, Minor DR, Lee CB, Albertini MR, Flaherty LE, Petrella TM, Streicher H, Sondak VK, Kirkwood JM
    • Issue date: 2021 May
    • Correlation between immune-related adverse events and prognosis in patients with gastric cancer treated with nivolumab.
    • Authors: Masuda K, Shoji H, Nagashima K, Yamamoto S, Ishikawa M, Imazeki H, Aoki M, Miyamoto T, Hirano H, Honma Y, Iwasa S, Okita N, Takashima A, Kato K, Boku N
    • Issue date: 2019 Oct 21
    DSpace software (copyright © 2002 - 2023)  DuraSpace
    Quick Guide | Contact Us
    Open Repository is a service operated by 
    Atmire NV
     

    Export search results

    The export option will allow you to export the current search results of the entered query to a file. Different formats are available for download. To export the items, click on the button corresponding with the preferred download format.

    By default, clicking on the export buttons will result in a download of the allowed maximum amount of items.

    To select a subset of the search results, click "Selective Export" button and make a selection of the items you want to export. The amount of items that can be exported at once is similarly restricted as the full export.

    After making a selection, click one of the export format buttons. The amount of items that will be exported is indicated in the bubble next to export format.