The Prognostic Impact of Gender, Therapeutic Strategies, Molecular Background, and Tumor-Infiltrating Lymphocytes in Glioblastoma: A Still Unsolved Jigsaw
Despite the adoption of novel therapeutical approaches, the outcomes for glioblastoma (GBM) patients remain poor. In the present study, we investigated the prognostic impact of several clinico-pathological and molecular features as well as the role of the cellular immune response in a series of 59 G...
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-02-01
|
| Series: | Genes |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2073-4425/14/2/501 |
| _version_ | 1797620824312643584 |
|---|---|
| author | Lorenzo Innocenti Valerio Ortenzi Rosa Scarpitta Nicola Montemurro Francesco Pasqualetti Roberta Asseri Stefano Lazzi Anna Szumera-Cieckiewicz Katia De Ieso Paolo Perrini Antonio Giuseppe Naccarato Cristian Scatena Giuseppe Nicolò Fanelli |
| author_facet | Lorenzo Innocenti Valerio Ortenzi Rosa Scarpitta Nicola Montemurro Francesco Pasqualetti Roberta Asseri Stefano Lazzi Anna Szumera-Cieckiewicz Katia De Ieso Paolo Perrini Antonio Giuseppe Naccarato Cristian Scatena Giuseppe Nicolò Fanelli |
| author_sort | Lorenzo Innocenti |
| collection | DOAJ |
| description | Despite the adoption of novel therapeutical approaches, the outcomes for glioblastoma (GBM) patients remain poor. In the present study, we investigated the prognostic impact of several clinico-pathological and molecular features as well as the role of the cellular immune response in a series of 59 GBM. CD4+ and CD8+ tumor-infiltrating lymphocytes (TILs) were digitally assessed on tissue microarray cores and their prognostic role was investigated. Moreover, the impact of other clinico-pathological features was evaluated. The number of CD4+ and CD8+ is higher in GBM tissue compared to normal brain tissue (<i>p</i> < 0.0001 and <i>p</i> = 0.0005 respectively). A positive correlation between CD4+ and CD8+ in GBM is present (<i>r<sub>s</sub> =</i> 0.417—<i>p</i> = 0.001). CD4+ TILs are inversely related to overall survival (OS) (HR = 1.79, 95% CI 1.1–3.1, <i>p =</i> 0.035). The presence of low CD4+ TILs combined with low CD8+ TILs is an independent predictor of longer OS (HR 0.38, 95% CI 0.18–0.79, <i>p =</i> 0.014). Female sex is independently related to longer OS (HR 0.42, 95% CI 0.22–0.77, <i>p =</i> 0.006). Adjuvant treatment, methylguanine methyltransferase (<i>MGMT</i>) promoter methylation, and age remain important prognostic factors but are influenced by other features. Adaptive cell-mediated immunity can affect the outcomes of GBM patients. Further studies are needed to elucidate the commitment of the CD4+ cells and the effects of different TILs subpopulations in GBM. |
| first_indexed | 2024-03-11T08:47:07Z |
| format | Article |
| id | doaj.art-9d3b608d86be47aa9a522fbb9866e430 |
| institution | Directory Open Access Journal |
| issn | 2073-4425 |
| language | English |
| last_indexed | 2024-03-11T08:47:07Z |
| publishDate | 2023-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Genes |
| spelling | doaj.art-9d3b608d86be47aa9a522fbb9866e4302023-11-16T20:43:50ZengMDPI AGGenes2073-44252023-02-0114250110.3390/genes14020501The Prognostic Impact of Gender, Therapeutic Strategies, Molecular Background, and Tumor-Infiltrating Lymphocytes in Glioblastoma: A Still Unsolved JigsawLorenzo Innocenti0Valerio Ortenzi1Rosa Scarpitta2Nicola Montemurro3Francesco Pasqualetti4Roberta Asseri5Stefano Lazzi6Anna Szumera-Cieckiewicz7Katia De Ieso8Paolo Perrini9Antonio Giuseppe Naccarato10Cristian Scatena11Giuseppe Nicolò Fanelli12Division of Pathology, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56126 Pisa, ItalyDepartment of Laboratory Medicine, Pisa University Hospital, 56126 Pisa, ItalyDivision of Pathology, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56126 Pisa, ItalyDepartment of Neurosurgery, Pisa University Hospital, 56126 Pisa, ItalyDepartment of Radiation Oncology, Pisa University Hospital, 56126 Pisa, ItalyDivision of Pathology, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56126 Pisa, ItalyAnatomic Pathology Unit, Department of Medical Biotechnology, University of Siena, 53100 Siena, ItalyDepartment of Pathology, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, PolandDepartment of Laboratory Medicine, Pisa University Hospital, 56126 Pisa, ItalyDepartment of Neurosurgery, Pisa University Hospital, 56126 Pisa, ItalyDivision of Pathology, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56126 Pisa, ItalyDivision of Pathology, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56126 Pisa, ItalyDivision of Pathology, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56126 Pisa, ItalyDespite the adoption of novel therapeutical approaches, the outcomes for glioblastoma (GBM) patients remain poor. In the present study, we investigated the prognostic impact of several clinico-pathological and molecular features as well as the role of the cellular immune response in a series of 59 GBM. CD4+ and CD8+ tumor-infiltrating lymphocytes (TILs) were digitally assessed on tissue microarray cores and their prognostic role was investigated. Moreover, the impact of other clinico-pathological features was evaluated. The number of CD4+ and CD8+ is higher in GBM tissue compared to normal brain tissue (<i>p</i> < 0.0001 and <i>p</i> = 0.0005 respectively). A positive correlation between CD4+ and CD8+ in GBM is present (<i>r<sub>s</sub> =</i> 0.417—<i>p</i> = 0.001). CD4+ TILs are inversely related to overall survival (OS) (HR = 1.79, 95% CI 1.1–3.1, <i>p =</i> 0.035). The presence of low CD4+ TILs combined with low CD8+ TILs is an independent predictor of longer OS (HR 0.38, 95% CI 0.18–0.79, <i>p =</i> 0.014). Female sex is independently related to longer OS (HR 0.42, 95% CI 0.22–0.77, <i>p =</i> 0.006). Adjuvant treatment, methylguanine methyltransferase (<i>MGMT</i>) promoter methylation, and age remain important prognostic factors but are influenced by other features. Adaptive cell-mediated immunity can affect the outcomes of GBM patients. Further studies are needed to elucidate the commitment of the CD4+ cells and the effects of different TILs subpopulations in GBM.https://www.mdpi.com/2073-4425/14/2/501glioblastomamicroenvironmentgenderTILsCD4CD8 |
| spellingShingle | Lorenzo Innocenti Valerio Ortenzi Rosa Scarpitta Nicola Montemurro Francesco Pasqualetti Roberta Asseri Stefano Lazzi Anna Szumera-Cieckiewicz Katia De Ieso Paolo Perrini Antonio Giuseppe Naccarato Cristian Scatena Giuseppe Nicolò Fanelli The Prognostic Impact of Gender, Therapeutic Strategies, Molecular Background, and Tumor-Infiltrating Lymphocytes in Glioblastoma: A Still Unsolved Jigsaw Genes glioblastoma microenvironment gender TILs CD4 CD8 |
| title | The Prognostic Impact of Gender, Therapeutic Strategies, Molecular Background, and Tumor-Infiltrating Lymphocytes in Glioblastoma: A Still Unsolved Jigsaw |
| title_full | The Prognostic Impact of Gender, Therapeutic Strategies, Molecular Background, and Tumor-Infiltrating Lymphocytes in Glioblastoma: A Still Unsolved Jigsaw |
| title_fullStr | The Prognostic Impact of Gender, Therapeutic Strategies, Molecular Background, and Tumor-Infiltrating Lymphocytes in Glioblastoma: A Still Unsolved Jigsaw |
| title_full_unstemmed | The Prognostic Impact of Gender, Therapeutic Strategies, Molecular Background, and Tumor-Infiltrating Lymphocytes in Glioblastoma: A Still Unsolved Jigsaw |
| title_short | The Prognostic Impact of Gender, Therapeutic Strategies, Molecular Background, and Tumor-Infiltrating Lymphocytes in Glioblastoma: A Still Unsolved Jigsaw |
| title_sort | prognostic impact of gender therapeutic strategies molecular background and tumor infiltrating lymphocytes in glioblastoma a still unsolved jigsaw |
| topic | glioblastoma microenvironment gender TILs CD4 CD8 |
| url | https://www.mdpi.com/2073-4425/14/2/501 |
| work_keys_str_mv | AT lorenzoinnocenti theprognosticimpactofgendertherapeuticstrategiesmolecularbackgroundandtumorinfiltratinglymphocytesinglioblastomaastillunsolvedjigsaw AT valerioortenzi theprognosticimpactofgendertherapeuticstrategiesmolecularbackgroundandtumorinfiltratinglymphocytesinglioblastomaastillunsolvedjigsaw AT rosascarpitta theprognosticimpactofgendertherapeuticstrategiesmolecularbackgroundandtumorinfiltratinglymphocytesinglioblastomaastillunsolvedjigsaw AT nicolamontemurro theprognosticimpactofgendertherapeuticstrategiesmolecularbackgroundandtumorinfiltratinglymphocytesinglioblastomaastillunsolvedjigsaw AT francescopasqualetti theprognosticimpactofgendertherapeuticstrategiesmolecularbackgroundandtumorinfiltratinglymphocytesinglioblastomaastillunsolvedjigsaw AT robertaasseri theprognosticimpactofgendertherapeuticstrategiesmolecularbackgroundandtumorinfiltratinglymphocytesinglioblastomaastillunsolvedjigsaw AT stefanolazzi theprognosticimpactofgendertherapeuticstrategiesmolecularbackgroundandtumorinfiltratinglymphocytesinglioblastomaastillunsolvedjigsaw AT annaszumeracieckiewicz theprognosticimpactofgendertherapeuticstrategiesmolecularbackgroundandtumorinfiltratinglymphocytesinglioblastomaastillunsolvedjigsaw AT katiadeieso theprognosticimpactofgendertherapeuticstrategiesmolecularbackgroundandtumorinfiltratinglymphocytesinglioblastomaastillunsolvedjigsaw AT paoloperrini theprognosticimpactofgendertherapeuticstrategiesmolecularbackgroundandtumorinfiltratinglymphocytesinglioblastomaastillunsolvedjigsaw AT antoniogiuseppenaccarato theprognosticimpactofgendertherapeuticstrategiesmolecularbackgroundandtumorinfiltratinglymphocytesinglioblastomaastillunsolvedjigsaw AT cristianscatena theprognosticimpactofgendertherapeuticstrategiesmolecularbackgroundandtumorinfiltratinglymphocytesinglioblastomaastillunsolvedjigsaw AT giuseppenicolofanelli theprognosticimpactofgendertherapeuticstrategiesmolecularbackgroundandtumorinfiltratinglymphocytesinglioblastomaastillunsolvedjigsaw AT lorenzoinnocenti prognosticimpactofgendertherapeuticstrategiesmolecularbackgroundandtumorinfiltratinglymphocytesinglioblastomaastillunsolvedjigsaw AT valerioortenzi prognosticimpactofgendertherapeuticstrategiesmolecularbackgroundandtumorinfiltratinglymphocytesinglioblastomaastillunsolvedjigsaw AT rosascarpitta prognosticimpactofgendertherapeuticstrategiesmolecularbackgroundandtumorinfiltratinglymphocytesinglioblastomaastillunsolvedjigsaw AT nicolamontemurro prognosticimpactofgendertherapeuticstrategiesmolecularbackgroundandtumorinfiltratinglymphocytesinglioblastomaastillunsolvedjigsaw AT francescopasqualetti prognosticimpactofgendertherapeuticstrategiesmolecularbackgroundandtumorinfiltratinglymphocytesinglioblastomaastillunsolvedjigsaw AT robertaasseri prognosticimpactofgendertherapeuticstrategiesmolecularbackgroundandtumorinfiltratinglymphocytesinglioblastomaastillunsolvedjigsaw AT stefanolazzi prognosticimpactofgendertherapeuticstrategiesmolecularbackgroundandtumorinfiltratinglymphocytesinglioblastomaastillunsolvedjigsaw AT annaszumeracieckiewicz prognosticimpactofgendertherapeuticstrategiesmolecularbackgroundandtumorinfiltratinglymphocytesinglioblastomaastillunsolvedjigsaw AT katiadeieso prognosticimpactofgendertherapeuticstrategiesmolecularbackgroundandtumorinfiltratinglymphocytesinglioblastomaastillunsolvedjigsaw AT paoloperrini prognosticimpactofgendertherapeuticstrategiesmolecularbackgroundandtumorinfiltratinglymphocytesinglioblastomaastillunsolvedjigsaw AT antoniogiuseppenaccarato prognosticimpactofgendertherapeuticstrategiesmolecularbackgroundandtumorinfiltratinglymphocytesinglioblastomaastillunsolvedjigsaw AT cristianscatena prognosticimpactofgendertherapeuticstrategiesmolecularbackgroundandtumorinfiltratinglymphocytesinglioblastomaastillunsolvedjigsaw AT giuseppenicolofanelli prognosticimpactofgendertherapeuticstrategiesmolecularbackgroundandtumorinfiltratinglymphocytesinglioblastomaastillunsolvedjigsaw |