Frontiers in Immunology (Jan 2023)

Perioperative corticosteroid treatment impairs tumor-infiltrating dendritic cells in patients with newly diagnosed adult-type diffuse gliomas

  • Claudia Carenza,
  • Claudia Carenza,
  • Sara Franzese,
  • Sara Franzese,
  • Alessandra Castagna,
  • Sara Terzoli,
  • Sara Terzoli,
  • Matteo Simonelli,
  • Matteo Simonelli,
  • Pasquale Persico,
  • Pasquale Persico,
  • Lorenzo Bello,
  • Lorenzo Bello,
  • Marco Conti Nibali,
  • Federico Pessina,
  • Federico Pessina,
  • Paolo Kunderfranco,
  • Clelia Peano,
  • Simone Balin,
  • Simone Balin,
  • Joanna Mikulak,
  • Francesca Calcaterra,
  • Francesca Calcaterra,
  • Raffaella Bonecchi,
  • Raffaella Bonecchi,
  • Benedetta Savino,
  • Benedetta Savino,
  • Massimo Locati,
  • Massimo Locati,
  • Silvia Della Bella,
  • Silvia Della Bella,
  • Domenico Mavilio,
  • Domenico Mavilio

DOI
https://doi.org/10.3389/fimmu.2022.1074762
Journal volume & issue
Vol. 13

Abstract

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IntroductionAdult-type diffuse gliomas are malignant primary brain tumors characterized by very poor prognosis. Dendritic cells (DCs) are key in priming antitumor effector functions in cancer, but their role in gliomas remains poorly understood.MethodsIn this study, we characterized tumor-infiltrating DCs (TIDCs) in adult patients with newly diagnosed diffuse gliomas by using multi-parametric flow cytometry and single-cell RNA sequencing.ResultsWe demonstrated that different subsets of DCs are present in the glioma microenvironment, whereas they are absent in cancer-free brain parenchyma. The largest cluster of TIDCs was characterized by a transcriptomic profile suggestive of severe functional impairment. Patients undergoing perioperative corticosteroid treatment showed a significant reduction of conventional DC1s, the DC subset with key functions in antitumor immunity. They also showed phenotypic and transcriptional evidence of a more severe functional impairment of TIDCs.DiscussionOverall, the results of this study indicate that functionally impaired DCs are recruited in the glioma microenvironment. They are severely affected by dexamethasone administration, suggesting that the detrimental effects of corticosteroids on DCs may represent one of the mechanisms contributing to the already reported negative prognostic impact of steroids on glioma patient survival.

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