PMID- 35069595 OWN - NLM STAT- MEDLINE DCOM- 20220307 LR - 20220307 IS - 1664-3224 (Electronic) IS - 1664-3224 (Linking) VI - 12 DP - 2021 TI - Myeloid Diagnostic and Prognostic Markers of Immune Suppression in the Blood of Glioma Patients. PG - 809826 LID - 10.3389/fimmu.2021.809826 [doi] LID - 809826 AB - BACKGROUND: Although gliomas are confined to the central nervous system, their negative influence over the immune system extends to peripheral circulation. The immune suppression exerted by myeloid cells can affect both response to therapy and disease outcome. We analyzed the expansion of several myeloid parameters in the blood of low- and high-grade gliomas and assessed their relevance as biomarkers of disease and clinical outcome. METHODS: Peripheral blood was obtained from 134 low- and high-grade glioma patients. CD14(+), CD14(+)/p-STAT3(+), CD14(+)/PD-L1(+), CD15(+) cells and four myeloid-derived suppressor cell (MDSC) subsets, were evaluated by flow cytometry. Arginase-1 (ARG1) quantity and activity was determined in the plasma. Multivariable logistic regression model was used to obtain a diagnostic score to discriminate glioma patients from healthy controls and between each glioma grade. A glioblastoma prognostic model was determined by multiple Cox regression using clinical and myeloid parameters. RESULTS: Changes in myeloid parameters associated with immune suppression allowed to define a diagnostic score calculating the risk of being a glioma patient. The same parameters, together with age, permit to calculate the risk score in differentiating each glioma grade. A prognostic model for glioblastoma patients stemmed out from a Cox multiple analysis, highlighting the role of MDSC, p-STAT3, and ARG1 activity together with clinical parameters in predicting patient's outcome. CONCLUSIONS: This work emphasizes the role of systemic immune suppression carried out by myeloid cells in gliomas. The identification of biomarkers associated with immune landscape, diagnosis, and outcome of glioblastoma patients lays the ground for their clinical use. CI - Copyright (c) 2022 Del Bianco, Pinton, Magri, Cane, Masetto, Basso, Padovan, Volpin, d'Avella, Lombardi, Zagonel, Bronte, Della Puppa and Mandruzzato. FAU - Del Bianco, Paola AU - Del Bianco P AD - Department of Oncology, Oncology 1, Veneto Institute of Oncology IOV-IRCCS, Padova, Italy. FAU - Pinton, Laura AU - Pinton L AD - Department of Oncology, Oncology 1, Veneto Institute of Oncology IOV-IRCCS, Padova, Italy. FAU - Magri, Sara AU - Magri S AD - Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy. FAU - Cane, Stefania AU - Cane S AD - University Hospital and Department of Medicine, Verona, Italy. FAU - Masetto, Elena AU - Masetto E AD - Department of Oncology, Oncology 1, Veneto Institute of Oncology IOV-IRCCS, Padova, Italy. FAU - Basso, Daniela AU - Basso D AD - Department of Medicine, University of Padova, Padova, Italy. FAU - Padovan, Marta AU - Padovan M AD - Department of Oncology, Oncology 1, Veneto Institute of Oncology IOV-IRCCS, Padova, Italy. FAU - Volpin, Francesco AU - Volpin F AD - University Hospital of Padova, Neurosurgery Department, Padova, Italy. FAU - d'Avella, Domenico AU - d'Avella D AD - Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy. AD - University Hospital of Padova, Neurosurgery Department, Padova, Italy. FAU - Lombardi, Giuseppe AU - Lombardi G AD - Department of Oncology, Oncology 1, Veneto Institute of Oncology IOV-IRCCS, Padova, Italy. FAU - Zagonel, Vittorina AU - Zagonel V AD - Department of Oncology, Oncology 1, Veneto Institute of Oncology IOV-IRCCS, Padova, Italy. FAU - Bronte, Vincenzo AU - Bronte V AD - University Hospital and Department of Medicine, Verona, Italy. FAU - Della Puppa, Alessandro AU - Della Puppa A AD - Neurosurgery, Department of NEUROFARBA, Careggi University Hospital, University of Florence, Florence, Italy. FAU - Mandruzzato, Susanna AU - Mandruzzato S AD - Department of Oncology, Oncology 1, Veneto Institute of Oncology IOV-IRCCS, Padova, Italy. AD - Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20220107 PL - Switzerland TA - Front Immunol JT - Frontiers in immunology JID - 101560960 RN - 0 (B7-H1 Antigen) RN - 0 (Biomarkers, Tumor) RN - 0 (CD274 protein, human) RN - 0 (STAT3 Transcription Factor) RN - 0 (STAT3 protein, human) RN - EC 3.5.3.1 (ARG1 protein, human) RN - EC 3.5.3.1 (Arginase) SB - IM MH - Adolescent MH - Adult MH - Aged MH - Aged, 80 and over MH - Arginase/blood MH - B7-H1 Antigen/blood MH - Biomarkers, Tumor/*blood MH - Female MH - Glioma/*blood/*diagnosis/etiology MH - Humans MH - Immunocompromised Host MH - Immunophenotyping MH - Leukocytes, Mononuclear/immunology/metabolism MH - Liquid Biopsy MH - Male MH - Middle Aged MH - Myeloid Cells/*immunology/*metabolism MH - Myeloid-Derived Suppressor Cells/immunology/metabolism MH - Neoplasm Grading MH - Neoplasm Staging MH - Prognosis MH - STAT3 Transcription Factor/blood MH - Young Adult PMC - PMC8777055 OTO - NOTNLM OT - STAT3 OT - arginase 1 (ARG1) OT - biomarkers OT - glioma OT - myeloid-derived suppressor cell 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- 2022/01/25 06:00 MHDA- 2022/03/08 06:00 PMCR- 2021/01/01 CRDT- 2022/01/24 08:49 PHST- 2021/11/05 00:00 [received] PHST- 2021/12/13 00:00 [accepted] PHST- 2022/01/24 08:49 [entrez] PHST- 2022/01/25 06:00 [pubmed] PHST- 2022/03/08 06:00 [medline] PHST- 2021/01/01 00:00 [pmc-release] AID - 10.3389/fimmu.2021.809826 [doi] PST - epublish SO - Front Immunol. 2022 Jan 7;12:809826. doi: 10.3389/fimmu.2021.809826. eCollection 2021.