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1.
Cancer Immunol Res ; 12(2): 232-246, 2024 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-38091354

RESUMO

Isocitrate dehydrogenase (IDH)-wild-type (WT) high-grade gliomas, especially glioblastomas, are highly aggressive and have an immunosuppressive tumor microenvironment. Although tumor-infiltrating immune cells are known to play a critical role in glioma genesis, their heterogeneity and intercellular interactions remain poorly understood. In this study, we constructed a single-cell transcriptome landscape of immune cells from tumor tissue and matching peripheral blood mononuclear cells (PBMC) from IDH-WT high-grade glioma patients. Our analysis identified two subsets of tumor-associated macrophages (TAM) in tumors with the highest protumorigenesis signatures, highlighting their potential role in glioma progression. We also investigated the T-cell trajectory and identified the aryl hydrocarbon receptor (AHR) as a regulator of T-cell dysfunction, providing a potential target for glioma immunotherapy. We further demonstrated that knockout of AHR decreased chimeric antigen receptor (CAR) T-cell exhaustion and improved CAR T-cell antitumor efficacy both in vitro and in vivo. Finally, we explored intercellular communication mediated by ligand-receptor interactions within the tumor microenvironment and PBMCs and revealed the unique cellular interactions present in the tumor microenvironment. Taken together, our study provides a comprehensive immune landscape of IDH-WT high-grade gliomas and offers potential drug targets for glioma immunotherapy.


Assuntos
Neoplasias Encefálicas , Glioma , Humanos , Isocitrato Desidrogenase/genética , Leucócitos Mononucleares/patologia , Perfilação da Expressão Gênica , Mutação , Microambiente Tumoral/genética
2.
Anal Cell Pathol (Amst) ; 2022: 2552397, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35866054

RESUMO

Medulloblastoma is one of the most common malignant tumors of the central nervous system in children. Although KIF2B was reported as an oncogene in several malignant tumor types, its role in medulloblastoma has not been studied so far. The PCR results of our study showed that KIF26B is highly expressed in medulloblastoma, and its high expression is associated with a high clinical stage. Knockdown the expression of KIF26B could significantly impair the proliferation and migration of medulloblastoma cells. KIF26B promotes the malignant progression of medulloblastoma by affecting the expression of phosphorylation of key proteins in the PI3K/AKT signaling pathway. With the help of 740 Y-P, activating the pi3k signaling pathway can partially rescue the phenotype. Therefore, our experimental results suggest that KIF26B is a potential target for medulloblastoma.


Assuntos
Neoplasias Cerebelares , Cinesinas , Meduloblastoma , Apoptose , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Neoplasias Cerebelares/genética , Neoplasias Cerebelares/metabolismo , Humanos , Cinesinas/genética , Meduloblastoma/genética , Meduloblastoma/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo
3.
Medicine (Baltimore) ; 98(21): e15737, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31124953

RESUMO

RATIONALE: Solitary fibrous tumors of central nervous system are rare spindle-cell mesenchymal tumors. Although most are benign in nature, malignant transformation and extracranial metastasis have been reported. Up to now, only one case of CSF dissemination was described. Here we described an extremely rare case of intracranial Solitary fibrous tumors arising from the pineal region with a delayed ectopic metastasis. PATIENT CONCERNS: A 35-year-old female presented with double vision, memory disturbance and unsteady gait was referred to our center. MRI showed an irregular mass in the pineal region. DIAGNOSES: The patient was diagnosed as pineal tumor, with unknown pathology. INTERVENTIONS: Gross total resection was achieved and the pathologic studies confirmed a solitary fibrous tumor. Thirty-nine months later local recurrence occurred and gamma-knife radiotherapy was offered. Seven months later, MRI found a metastasis in the left temporal lobe. Surgical resection was conducted and pathological analysis revealed changes in cell morphology, counts and Ki-67 level, confirmed the diagnosis of solitary fibrous tumor/hemangiopericytoma (WHO Grade III). The patient received post-operational radiotherapy. OUTCOMES: The patient was followed up for 7 months with no signs of recurrence. LESSONS: Here, we report an extremely rare case of primary solitary fibrous tumor of pineal region with delayed intracranial ectopic metastasis, together with literature review of metastatic solitary fibrous tumors. Strict surveillance is strongly recommended, considering the malignant potential of this seemingly benign disease entity. Complete resection of the tumor is the treatment of first choice and radiotherapy might be an effective adjuvant therapy for high grade SFT/HPCs.


Assuntos
Neoplasias Encefálicas/patologia , Glândula Pineal/patologia , Tumores Fibrosos Solitários/patologia , Adulto , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/terapia , Feminino , Humanos , Metástase Neoplásica , Recidiva Local de Neoplasia , Tumores Fibrosos Solitários/diagnóstico , Tumores Fibrosos Solitários/terapia
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