Phenotypic characterization of human peripheral γδT-cell subsets in glioblastoma.

The antitumoral contribution of γδT cells depends on their activation and differentiation into effectors. This depends on different molecules and membrane receptors, which conditions their physiology. This study aimed to determine the phenotypic characteristics of γδT cells in glioblastoma (GBM) according to five layers of membrane receptors. Among ten GBM cases initially enrolled, five of them who had been confirmed by pathological examination and ten healthy controls underwent phenotyping of peripheral γδT cells by flow cytometry, using the following staining: αßTCR, γδTCR, CD3, CD4, CD8, CD16, CD25, CD27, CD28, CD45, CD45RA, CD56, NKG2D, CD272(BTLA), and CD279(PD-1). Compared with the controls, the results showed no significant change in the number of γδT cells. However, there was a decrease of double-negative (CD4- CD8- ) Tγδ cells and an increase of naive γδT cells, a lack of CD25 expression, a decrease of the expression of CD279, and a remarkable, but not significant, increase in the expression of the CD27 and CD28 costimulation markers. Among the γδT cell subsets, the number of Vδ2 decreased in glioblastoma and showed no significant difference in the expression of CD16, CD56, and NKG2D. In contrast, the number of Vδ1 increased in glioblastoma with overexpression of CD16, CD56, and NKG2D. Our results showed that γδT cells are prone to adopt a pro-inflammatory profile in the glioblastoma context, which suggests that they might be a potential tool to consider in T cell-based immunotherapy in glioblastoma. However, this requires additional investigation on a larger sample size.

Immune tumoral microenvironment in gliomas: focus on CD3+ T cells, Vδ1+ T cells, and microglia/macrophages.

Gliomas are histologically defined as low-grade gliomas (LGG) and high-grade gliomas (HGG). The most common type of HGG is the glioblastoma (GBM). We aimed to determine the immunological characteristics of CD3 T-cells, Vδ1 T-cells, and microglia/macrophages infiltrating brain gliomas. We collected 24 formalin-fixed paraffin-embedded samples issued from 19 cases of GBM and 5 cases of LGG. An immunohistochemical analysis was performed using anti-CD3, anti-Vδ1, and anti-iba-1 antibodies. Labelling indexes (LI) of CD3 and Vδ1 were evaluated quantitatively, and other CD3, Vδ1, and iba-1 staining characteristics were evaluated qualitatively. The median age of patients was 49 years in GBM and 52 years in LGG. The sex ratio was 1.4 and GBM predominated in males (p = 0.05). In GBM, the medians of CD3-LI and Vδ1-LI were 30 and 3.5 respectively. CD3-LI inversely correlated with survival in GBM cases (r = - 0.543; p = 0.016). CD3 staining intensity correlated with CD3-LI (p < 0.0001) and with the survival in GBM cases (p = 0.003). Compared to LGG, the CD3-LI, the intensity of intra-tumoral Vδ1 staining, and the amount of iba-1 were higher in GBM (p = 0.042; p = 0.014; and p = 0.001 respectively). The iba-1 organization was more amoeboid in older patients and more branched in younger patients (p = 0.028) and tended to be more amoeboid in cases with high iba-1 amount (p = 0.09). Our results suggest that a high level of CD3-LI and a strong intra-tumoral infiltration of Vδ1 T-cells as well as a high involvement of TAM can be considered potential markers of poor prognosis of GBM. However, this requires further studies on more balanced GBM-LGG sample, including an expanded panel of biomarkers.

[Epidemiological, clinical, therapeutic and evolutionary features of patients with glioblastoma: series of cases managed in the Department of Hematology-Oncology at the Mohammed VI University Hospital Center in Marrakech in 2016 and 2017]. / Caractéristiques épidémiologiques, cliniques, thérapeutiques et évolutives des patients atteints de glioblastome cérébral: série de cas pris en charge au centre d´oncohématologie du Centre Hospitalier Universitaire Mohammed VI de Marrakech en 2016 et 2017.

Glioblastoma is the most common primary malignant brain tumour. Despite advances in diagnostic and therapeutic treatments, it is still associated with poor outcome The purpose of this study of cases is to describe the epidemiological, clinical, therapeutic and evolutionary features of patients with glioblastoma admitted to the Department of Hematology-Oncology (DHO) in Marrakech in 2016 and 2017. We conducted a literature review of epidemiological, clinical, radiological, anatomopathological, therapeutic and evolutionary data from 40 patients. Glioblastoma accounted for 47.6% of treated intracranial tumours. The average age of patients was 52.4±12.3 years. Functional impotence and signs of intracranial hypertension were the main symptoms. Tumours mainly occurred in the parietal region (44%) and were large (57.5%). Aphasia was related to tumour size (p=0.042). Nine cases had glioblastomas-IDH1-wild and one case had glioblastoma-IDH1-mutant. On admission, patients had poor performance-status. This was due to a prolonged time between surgery and DHO admission (p= 0.034). Patients with sensory impairments were older (62.5±3 years) than those without sensory impairments (51.2±12 years) (p=0,045). In-patient women received chemoradiotherapy (1.5±1 month) earlier than men (2.3±1.2 months) (p=0.03). Survival was 13.6±5.3 months; it was unrelated to the time to surgery (p=0.076), the time to DHO (p=0.058), and the time to chemoradiotherapy (p=0.073). The epidemiological, clinical, radiological and evolutionary features of our sample were comparable to literature data. The molecular profiling was not systematically realized. Despite prolonged treatment times, no link to survival was detected.