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    T cell immune awakening in response to immunotherapy is age-dependent

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    Authors
    Salih, Z.
    Banyard, A.
    Tweedy, J.
    Galvani, E.
    Middlehurst, P.
    Mills, S.
    Weightman, J.
    Gupta, A.
    Lorigan, P. C.
    Zhou, C.
    Dhomen, N.
    Valpione, S.
    Marais, R.
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    Affiliation
    Molecular Oncology Group, Cancer Research UK Manchester Institute, The University of Manchester, Alderley Park, Macclesfield, Cheshire SK10 4TG, United Kingdom
    Issue Date
    2021
    
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    Abstract
    Background Precision immuno-oncology approaches are needed to improve cancer care. We recently demonstrated that in patients with metastatic melanoma, an increase of clonality or diversity of the T cell receptor (TCR) repertoire of peripheral T cells following one cycle of immunotherapy is coincident with response to immune-checkpoint blockade (ICB). We also identified a subset of peripheral CD8+ immune-effector memory T cells (TIE cells) whose expansion was associated with response to ICB and increased overall survival. To improve our understanding of peripheral T cell dynamics, we examined the clinical correlates associated with these immune signatures. Methods Fifty patients with metastatic melanoma treated with first-line anti-PD-1 ICB were included. We analysed TCR repertoire and peripheral TIE cell dynamics by age before treatment (T0) and after the first cycle of treatment at week 3 (W3). Results We observed a correlation between TIE abundance and age at T0 (r = 0.40), which reduced following treatment at W3 (r = 0.07). However, at W3, we observed two significantly opposing patterns (p = 0.03) of TCR repertoire rearrangement in patients who responded to treatment, with patients ≥70 years of age showing an increase in TCR clonality and patients <70 years of age showing an increase in TCR diversity. Conclusions We demonstrate that immunotherapy-induced immune-awakening patterns in patients with melanoma are age-related and may impact patient response to ICB, and thus have implications for biomarker development and planning of personalised therapeutic strategies.
    Citation
    Salih Z, Banyard A, Tweedy J, Galvani E, Middlehurst P, Mills S, et al. T cell immune awakening in response to immunotherapy is age-dependent. Eur J Cancer. 2021;162:11-21.
    Journal
    Eur J Cancer
    URI
    http://hdl.handle.net/10541/625002
    DOI
    10.1016/j.ejca.2021.11.015
    PubMed ID
    34952479
    Additional Links
    https://dx.doi.org/10.1016/j.ejca.2021.11.015
    Type
    Article
    Language
    en
    ae974a485f413a2113503eed53cd6c53
    10.1016/j.ejca.2021.11.015
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