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    Low CD8 T cell counts predict benefit from hypoxia-modifying therapy in muscle-invasive bladder cancer

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    Authors
    Smith, Vicky
    Mukherjee, Debayan
    Tsakiroglou, Anna Maria
    Baker, Alexander
    Mistry, Hitesh
    Choudhury, Ananya
    Hoskin, Peter J
    Illidge, Timothy M
    West, Catharine M L
    Affiliation
    Division of Cancer Sciences, University of Manchester, Manchester M13 9PL, UK
    Issue Date
    2022
    
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    Abstract
    Background: As hypoxia can drive an immunosuppressive tumour microenvironment and inhibit CD8+ T cells, we investigated if patients with low tumour CD8+ T cells benefitted from hypoxia-modifying therapy. Methods: BCON was a phase III trial that randomised patients with muscle-invasive bladder cancer (MIBC) to radiotherapy alone or with hypoxia-modifying carbogen plus nicotinamide (CON). Tissue microarrays of diagnostic biopsies from 116 BCON patients were stained using multiplex immunohistochemistry (IHC) with the markers CD8, CD4, FOXP3, CD68 and PD-L1, plus DAPI. Hypoxia was assessed using CA9 IHC (n = 111). Linked transcriptomic data (n = 80) identified molecular subtype. Relationships with overall survival (OS) were investigated using Cox proportional hazard models. Results: High (upper quartile) vs. low CD8 T cell counts associated with a better OS across the whole cohort at 16 years (n = 116; HR 0.47, 95% CI 0.28-0.78, p = 0.003) and also in the radiotherapy alone group (n = 61; HR 0.39, 95% CI 0.19-0.76, p = 0.005). Patients with low CD8+ T cells benefited from CON (n = 87; HR 0.63, 95% CI 0.4-1.0, p = 0.05), but those with high CD8 T cells did not (n = 27; p = 0.95). CA9 positive tumours had fewer CD8+ T cells (p = 0.03). Prognostic significance of low CD8+ T cells in the whole cohort remained after adjusting for clinicopathologic variables. Basal vs. luminal subtype had more CD8+ cells (p = 0.02) but was not prognostic (n = 80; p = 0.26). Exploratory analyses with other immune markers did not improve on findings obtained with CD8 counts. Conclusions: MIBC with low CD8+ T cell counts may benefit from hypoxia-modifying treatment.
    Citation
    Smith V, Mukherjee D, Tsakiroglou AM, Baker A, Mistry H, Choudhury A, et al. Low CD8 T Cell Counts Predict Benefit from Hypoxia-Modifying Therapy in Muscle-Invasive Bladder Cancer. Cancers (Basel). 2022 Dec 21;15(1). PubMed PMID: 36612036. Pubmed Central PMCID: PMC9817934. Epub 2023/01/09. eng.
    Journal
    Cancers
    URI
    http://hdl.handle.net/10541/625944
    DOI
    10.3390/cancers15010041
    PubMed ID
    36612036
    Additional Links
    https://dx.doi.org/10.3390/cancers15010041
    Type
    Article
    Language
    en
    ae974a485f413a2113503eed53cd6c53
    10.3390/cancers15010041
    Scopus Count
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