PMID- 36703985 OWN - NLM STAT- MEDLINE DCOM- 20230130 LR - 20230202 IS - 1664-3224 (Electronic) IS - 1664-3224 (Linking) VI - 13 DP - 2022 TI - Perioperative corticosteroid treatment impairs tumor-infiltrating dendritic cells in patients with newly diagnosed adult-type diffuse gliomas. PG - 1074762 LID - 10.3389/fimmu.2022.1074762 [doi] LID - 1074762 AB - INTRODUCTION: Adult-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. METHODS: In 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. RESULTS: We 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. DISCUSSION: Overall, 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. CI - Copyright (c) 2023 Carenza, Franzese, Castagna, Terzoli, Simonelli, Persico, Bello, Nibali, Pessina, Kunderfranco, Peano, Balin, Mikulak, Calcaterra, Bonecchi, Savino, Locati, Della Bella and Mavilio. FAU - Carenza, Claudia AU - Carenza C AD - Department of Medical Biotechnologies and Translational Medicine, University of Milan, Milan, Italy. AD - Laboratory of Clinical and Experimental Immunology, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy. FAU - Franzese, Sara AU - Franzese S AD - Department of Medical Biotechnologies and Translational Medicine, University of Milan, Milan, Italy. AD - Laboratory of Clinical and Experimental Immunology, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy. FAU - Castagna, Alessandra AU - Castagna A AD - Laboratory of Leukocyte Biology, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy. FAU - Terzoli, Sara AU - Terzoli S AD - Laboratory of Clinical and Experimental Immunology, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy. AD - Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy. FAU - Simonelli, Matteo AU - Simonelli M AD - Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy. AD - Department of Medical Oncology and Hematology, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy. FAU - Persico, Pasquale AU - Persico P AD - Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy. AD - Department of Medical Oncology and Hematology, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy. FAU - Bello, Lorenzo AU - Bello L AD - Unit of Oncological Neurosurgery, IRCCS Istituto Ortopedico Galeazzi, Milan, Italy. AD - Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy. FAU - Nibali, Marco Conti AU - Nibali MC AD - Unit of Oncological Neurosurgery, IRCCS Istituto Ortopedico Galeazzi, Milan, Italy. FAU - Pessina, Federico AU - Pessina F AD - Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy. AD - Department of Neurosurgery, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy. FAU - Kunderfranco, Paolo AU - Kunderfranco P AD - Bioinformatics Unit, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy. FAU - Peano, Clelia AU - Peano C AD - Institute of Genetic and Biomedical Research, UoS Milan, National Research Council, Rozzano, Milan, Italy. FAU - Balin, Simone AU - Balin S AD - Department of Medical Biotechnologies and Translational Medicine, University of Milan, Milan, Italy. AD - Laboratory of Clinical and Experimental Immunology, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy. FAU - Mikulak, Joanna AU - Mikulak J AD - Laboratory of Clinical and Experimental Immunology, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy. FAU - Calcaterra, Francesca AU - Calcaterra F AD - Department of Medical Biotechnologies and Translational Medicine, University of Milan, Milan, Italy. AD - Laboratory of Clinical and Experimental Immunology, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy. FAU - Bonecchi, Raffaella AU - Bonecchi R AD - Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy. AD - Laboratory of Chemokine Biology, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy. FAU - Savino, Benedetta AU - Savino B AD - Department of Medical Biotechnologies and Translational Medicine, University of Milan, Milan, Italy. AD - Laboratory of Leukocyte Biology, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy. FAU - Locati, Massimo AU - Locati M AD - Department of Medical Biotechnologies and Translational Medicine, University of Milan, Milan, Italy. AD - Laboratory of Leukocyte Biology, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy. FAU - Della Bella, Silvia AU - Della Bella S AD - Department of Medical Biotechnologies and Translational Medicine, University of Milan, Milan, Italy. AD - Laboratory of Clinical and Experimental Immunology, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy. FAU - Mavilio, Domenico AU - Mavilio D AD - Department of Medical Biotechnologies and Translational Medicine, University of Milan, Milan, Italy. AD - Laboratory of Clinical and Experimental Immunology, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20230110 PL - Switzerland TA - Front Immunol JT - Frontiers in immunology JID - 101560960 RN - 0 (Adrenal Cortex Hormones) SB - IM MH - Humans MH - Adult MH - *Glioma MH - Prognosis MH - *Brain Neoplasms/drug therapy/pathology MH - Adrenal Cortex Hormones/therapeutic use MH - Dendritic Cells MH - Tumor Microenvironment PMC - PMC9872516 OTO - NOTNLM OT - brain tumors OT - dendritic cells OT - immune suppressive tumor microenvironment OT - perioperative corticosteroids OT - single cell-RNA sequencing COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2023/01/28 06:00 MHDA- 2023/01/31 06:00 PMCR- 2022/01/01 CRDT- 2023/01/27 02:18 PHST- 2022/10/19 00:00 [received] PHST- 2022/12/22 00:00 [accepted] PHST- 2023/01/27 02:18 [entrez] PHST- 2023/01/28 06:00 [pubmed] PHST- 2023/01/31 06:00 [medline] PHST- 2022/01/01 00:00 [pmc-release] AID - 10.3389/fimmu.2022.1074762 [doi] PST - epublish SO - Front Immunol. 2023 Jan 10;13:1074762. doi: 10.3389/fimmu.2022.1074762. eCollection 2022.