Tumor cell and immune cell profiles in primary human glioblastoma: Impact on patient outcome

Autor: Javie Ortiz, Laura Ruíz Martín, Alberto Orfao, Luis Torres Carretero, Maria Almeida, María González-Tablas Pimenta, Daniel Ángel Arandia Guzmán, Juan Carlos Roa Montes de Oca, María Dolores Tabernero, Adelaida Nieto, Álvaro Otero, Andoni García-Martín, Pablo Sousa-Casasnovas, Javier Villaseñor-Ledezma, Daniel Pascual-Argente
Přispěvatelé: Instituto de Salud Carlos III, Ministerio de Economía y Competitividad (España), European Commission, Junta de Castilla y León
Rok vydání: 2020
Předmět:
0301 basic medicine
Male
lymphocytes
Myeloid
Neutrophils
microglia
0302 clinical medicine
Tumor-Associated Macrophages
Tumor Microenvironment
IL-2 receptor
Lymphocytes
Research Articles
CD20
Aged
80 and over
education.field_of_study
biology
Brain Neoplasms
General Neuroscience
Immune cells
Middle Aged
medicine.anatomical_structure
myeloid cells
Myeloid cells
Female
Microglia
Research Article
Adult
Microenvironment
CD3
Population
CD19
Pathology and Forensic Medicine
03 medical and health sciences
Immune system
Lymphocytes
Tumor-Infiltrating
immune cells
medicine
Biomarkers
Tumor
Humans
education
Aged
business.industry
Myeloid-Derived Suppressor Cells
glioblastoma
microenvironment
030104 developmental biology
Cancer research
biology.protein
Neurology (clinical)
business
Glioblastoma
030217 neurology & neurosurgery
CD8
Zdroj: Brain Pathology
Digital.CSIC. Repositorio Institucional del CSIC
instname
ISSN: 1750-3639
Popis: © 2020 The Authors.
The distribution and role of tumor-infiltrating leucocytes in glioblastoma (GBM) remain largely unknown. Here, we investigated the cellular composition of 55 primary (adult) GBM samples by flow cytometry and correlated the tumor immune profile with patient features at diagnosis and outcome. GBM single-cell suspensions were stained at diagnosis (n = 44) and recurrence following radiotherapy and chemotherapy (n = 11) with a panel of 8-color monoclonal antibody combinations for the identification and enumeration of (GFAPCD45) tumor and normal astrocytic cells, infiltrating myeloid cells —i.e. microglial and blood-derived tumor-associated macrophages (TAM), M1-like, and M2-like TAM, neutrophils. and myeloid-derived suppressor cells (MDSC)— and tumor-infiltrating lymphocytes (TIL) —i.e. CD3T-cells and their TCD4, TCD8, TCD4CD8, and (CD25CD127) regulatory (T-regs) subsets, (CD19CD20) B-cells, and (CD16) NK-cells—. Overall, GBM samples consisted of a major population (mean ± 1SD) of tumor and normal astrocytic cells (73% ± 16%) together with a significant but variable fraction of immune cells (24% ± 18%). Within myeloid cells, TAM predominated (13% ± 12%) including both microglial cells (10% ± 11%) and blood-derived macrophages (3% ± 5%), in addition to a smaller proportion of neutrophils (5% ± 9%) and MDSC (4% ± 8%). Lymphocytes were less represented and mostly included TCD4 (0.5% ± 0.7%) and TCD8 cells (0.6% ± 0.7%), together with lower numbers of TCD4CD8 T-cells (0.2% ± 0.4%), T-regs (0.1% ± 0.2%), B-lymphocytes (0.1% ± 0.2%) and NK-cells (0.05% ± 0.05%). Overall, three distinct immune profiles were identified: cases with a minor fraction of leucocytes, tumors with a predominance of TAM and neutrophils, and cases with mixed infiltration by TAM, neutrophils, and T-lymphocytes. Untreated GBM patients with mixed myeloid and lymphoid immune infiltrates showed a significantly shorter patient overall survival versus the other two groups, in the absence of gains of the EGFR gene (p = 0.02). Here we show that immune cell infiltrates are systematically present in GBM, with highly variable levels and immune profiles. Patients with mixed myeloid and T-lymphoid infiltrates showed a worse outcome.
Instituto de Salud Carlos III, Ministerio de Economía y Competitividad, Madrid, Spain and fondos FEDER, Grant/Award Number: CB16/12/00400 and ISCIII PI16/0476; Consejería de Sanidad Junta de Castilla y León, Gerencia Regional de Salud, Spain, Grant/Award Number: GRS2049/A/19
Databáze: OpenAIRE
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