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Immune cell infiltration and inflammatory landscape in primary brain tumours.
Luce, Amalia; Abate, Marianna; Scognamiglio, Giosuè; Montella, Marco; Iervolino, Domenico; Campione, Severo; Di Mauro, Annabella; Sepe, Orlando; Gigantino, Vincenzo; Tathode, Madhura S; Ferrara, Gerardo; Monaco, Roberto; De Dominicis, Gianfranco; Misso, Gabriella; Gentile, Vittorio; Franco, Renato; Zappavigna, Silvia; Caraglia, Michele.
Afiliação
  • Luce A; Department of Precision Medicine, University of Campania "Luigi Vanvitelli", Via L. De Crecchio, 7, 80138, Naples, Italy.
  • Abate M; Department of Precision Medicine, University of Campania "Luigi Vanvitelli", Via L. De Crecchio, 7, 80138, Naples, Italy.
  • Scognamiglio G; Laboratory of Precision and Molecular Oncology, Biogem Scarl, Institute of Genetic Research, 83031, Ariano Irpino, Italy.
  • Montella M; Pathological Anatomy and Cytopathology Unit, Istituto Nazionale Tumori, IRCCS Fondazione G. Pascale, 80131, Naples, Italy.
  • Iervolino D; Department of Mental and Physical Health and Preventive Medicine, Pathology Unit, University of Campania "Luigi Vanvitelli", 80138, Naples, Italy.
  • Campione S; Pathological Anatomy and Cytopathology Unit, Istituto Nazionale Tumori, IRCCS Fondazione G. Pascale, 80131, Naples, Italy.
  • Di Mauro A; Department of Advanced Technology, Pathology Unit, Cardarelli Hospital, 80131, Naples, Italy.
  • Sepe O; Pathological Anatomy and Cytopathology Unit, Istituto Nazionale Tumori, IRCCS Fondazione G. Pascale, 80131, Naples, Italy.
  • Gigantino V; Pathological Anatomy and Cytopathology Unit, Istituto Nazionale Tumori, IRCCS Fondazione G. Pascale, 80131, Naples, Italy.
  • Tathode MS; Pathological Anatomy and Cytopathology Unit, Istituto Nazionale Tumori, IRCCS Fondazione G. Pascale, 80131, Naples, Italy.
  • Ferrara G; Department of Precision Medicine, University of Campania "Luigi Vanvitelli", Via L. De Crecchio, 7, 80138, Naples, Italy.
  • Monaco R; Pathological Anatomy and Cytopathology Unit, Istituto Nazionale Tumori, IRCCS Fondazione G. Pascale, 80131, Naples, Italy.
  • De Dominicis G; Department of Advanced Technology, Pathology Unit, Cardarelli Hospital, 80131, Naples, Italy.
  • Misso G; Department of Advanced Technology, Pathology Unit, Cardarelli Hospital, 80131, Naples, Italy.
  • Gentile V; Department of Precision Medicine, University of Campania "Luigi Vanvitelli", Via L. De Crecchio, 7, 80138, Naples, Italy.
  • Franco R; Department of Precision Medicine, University of Campania "Luigi Vanvitelli", Via L. De Crecchio, 7, 80138, Naples, Italy.
  • Zappavigna S; Department of Mental and Physical Health and Preventive Medicine, Pathology Unit, University of Campania "Luigi Vanvitelli", 80138, Naples, Italy.
  • Caraglia M; Department of Precision Medicine, University of Campania "Luigi Vanvitelli", Via L. De Crecchio, 7, 80138, Naples, Italy. silvia.zappavigna@unicampania.it.
J Transl Med ; 22(1): 521, 2024 May 30.
Article em En | MEDLINE | ID: mdl-38816839
ABSTRACT

BACKGROUND:

Primary malignant brain tumours are more than one-third of all brain tumours and despite the molecular investigation to identify cancer driver mutations, the current therapeutic options available are challenging due to high intratumour heterogeneity. In addition, an immunosuppressive and inflammatory tumour microenvironment strengthens cancer progression. Therefore, we defined an immune and inflammatory profiling of meningioma and glial tumours to elucidate the role of the immune infiltration in these cancer types.

METHODS:

Using tissue microarrays of 158 brain tumour samples, we assessed CD3, CD4, CD8, CD20, CD138, Granzyme B (GzmB), 5-Lipoxygenase (5-LOX), Programmed Death-Ligand 1 (PD-L1), O-6-Methylguanine-DNA Methyltransferase (MGMT) and Transglutaminase 2 (TG2) expression by immunohistochemistry (IHC). IHC results were correlated using a Spearman correlation matrix. Transcript expression, correlation, and overall survival (OS) analyses were evaluated using public datasets available on GEPIA2 in Glioblastoma (GBM) and Lower Grade Glioma (LGG) cohorts.

RESULTS:

Seven out of ten markers showed a significantly different IHC expression in at least one of the evaluated cohorts whereas CD3, CD4 and 5-LOX were differentially expressed between GBMs and astrocytomas. Correlation matrix analysis revealed that 5-LOX and GzmB expression were associated in both meningiomas and GBMs, whereas 5-LOX expression was significantly and positively correlated to TG2 in both meningioma and astrocytoma cohorts. These findings were confirmed with the correlation analysis of TCGA-GBM and LGG datasets. Profiling of mRNA levels indicated a significant increase in CD3 (CD3D, CD3E), and CD138 (SDC1) expression in GBM compared to control tissues. CD4 and 5-LOX (ALOX5) mRNA levels were significantly more expressed in tumour samples than in normal tissues in both GBM and LGG. In GBM cohort, GzmB (GZMB), SDC1 and MGMT gene expression predicted a poor overall survival (OS). Moreover, in LGG cohort, an increased expression of CD3 (CD3D, CD3E, CD3G), CD8 (CD8A), GZMB, CD20 (MS4A1), SDC1, PD-L1, ALOX5, and TG2 (TGM2) genes was associated with worse OS.

CONCLUSIONS:

Our data have revealed that there is a positive and significant correlation between the expression of 5-LOX and GzmB, both at RNA and protein level. Further evaluation is needed to understand the interplay of 5-LOX and immune infiltration in glioma progression.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias Encefálicas / Inflamação Limite: Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias Encefálicas / Inflamação Limite: Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Ano de publicação: 2024 Tipo de documento: Article