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CD8+CD103+PD1+TIM3+ T cells in glioblastoma microenvironment correlate with prognosis.
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  • Lucia Gabriele,
  • Giulia Romagnoli,
  • Quintino Giorgio D'Alessandris,
  • Imerio Capone,
  • Andrea Tavilla,
  • Irene Canini,
  • Caterina Lapenta,
  • Mariachiara Buccarelli,
  • Martina Giordano,
  • Valentina Tirelli,
  • Massimo Sanchez,
  • Alessandra Fragale,
  • Stefano Giannetti,
  • Rina Di Bonaventura,
  • Liverana Lauretti,
  • Mauro Biffoni,
  • Lucia Ricci-Vitiani,
  • Roberto Pallini
Lucia Gabriele
Istituto Superiore Di Sanita Dipartimento di Ematologia oncologia e medicina molecolare

Corresponding Author:[email protected]

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Giulia Romagnoli
Istituto Superiore Di Sanita Dipartimento di Ematologia oncologia e medicina molecolare
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Quintino Giorgio D'Alessandris
Universita Cattolica del Sacro Cuore - Campus di Roma
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Imerio Capone
Istituto Superiore Di Sanita Dipartimento di Ematologia oncologia e medicina molecolare
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Andrea Tavilla
Istituto Superiore di Sanita
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Irene Canini
Istituto Superiore Di Sanita Dipartimento di Ematologia oncologia e medicina molecolare
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Caterina Lapenta
Istituto Superiore Di Sanita Dipartimento di Ematologia oncologia e medicina molecolare
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Mariachiara Buccarelli
Istituto Superiore Di Sanita Dipartimento di Ematologia oncologia e medicina molecolare
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Martina Giordano
Universita Cattolica del Sacro Cuore - Campus di Roma
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Valentina Tirelli
Istituto Superiore di Sanita
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Massimo Sanchez
Istituto Superiore di Sanita
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Alessandra Fragale
Istituto Superiore Di Sanita Dipartimento di Ematologia oncologia e medicina molecolare
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Stefano Giannetti
Universita Cattolica del Sacro Cuore - Campus di Roma
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Rina Di Bonaventura
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
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Liverana Lauretti
Universita Cattolica del Sacro Cuore - Campus di Roma
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Mauro Biffoni
Istituto Superiore Di Sanita Dipartimento di Ematologia oncologia e medicina molecolare
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Lucia Ricci-Vitiani
Istituto Superiore Di Sanita Dipartimento di Ematologia oncologia e medicina molecolare
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Roberto Pallini
Universita Cattolica del Sacro Cuore - Campus di Roma
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Abstract

Glioblastoma (GBM) is the most common and aggressive brain tumor with poor outcome. Immune checkpoint inhibitors (ICIs) have been tested in GBM and, despite disappointing results, the identification of a small subgroup of responders underlies the need to improve our understanding of the tumor microenvironment (TME) immunity. The aim of this study was to determine whether the expression of selected immune checkpoints on tissue-resident memory T cells (Trm) may predict patient outcome. We conducted a single cohort observational study. Tumor samples were collected from 45 patients with histologically confirmed, IDH wild type, GBM (WHO grade IV) and processed to obtain single cell suspensions. Using multiparametric flow cytometry and uni/multivariate analyses, patients were assessed for the correlation of Trm with overall survival (OS) and progression-free survival (PFS). High and low frequency of Trm expressing PD1 and TIM3 was found to be linked to clinical outcome. In fact, low frequency of Trm expressing PD1 or TIM3 or both markers defined subgroups as independent positive prognostic factors for patient survival. On multivariate analysis, low CD8+CD103+PD1+TIM3+ Trm and KPS ≥70 were confirmed to be the most predictive independent factors associated with longer OS (HR [95%CI]: 0.14 [0.04 - 0.52] p˂0.001, 0.39 [0.16 - 0.96] p=0.04, respectively). The CD8+CD103+ Trm subgroups also resulted age-linked predictors for survival in GBM.
09 Oct 20231st Revision Received
09 Oct 2023Submission Checks Completed
09 Oct 2023Assigned to Editor
09 Oct 2023Review(s) Completed, Editorial Evaluation Pending
10 Oct 2023Editorial Decision: Accept