RESUMEN
Glioblastoma is the most common malignant primary brain tumor in adults. The prognosis is extremely poor even with standard treatment of maximal safe resection, radiotherapy, and chemotherapy. Recurrence is inevitable within months, and treatment options are very limited. Chimeric antigen receptor T-cell therapy (CART) and bispecific T-cell engagers (TCEs) are two emerging immunotherapies that can redirect T-cells for tumor-specific killing and have shown remarkable success in hematological malignancies and been under extensive study for application in glioblastoma. While there have been multiple clinical trials showing preliminary evidence of safety and efficacy for CART, bispecific TCEs are still in the early stages of clinical testing, with preclinical studies showing very promising results. However, there are multiple shared challenges that need to be addressed in the future, including the route of delivery, antigen escape, the immunosuppressive tumor microenvironment, and toxicity resulting from the limited choice of tumor-specific antigens. Efforts are underway to optimize the design of both these treatments and find the ideal combination therapy to overcome these challenges. In this review, we describe the work that has been performed as well as novel approaches in glioblastoma and in other solid tumors that may be applicable in the future.
RESUMEN
Single-cell technologies have enabled the characterization of the tumour microenvironment at unprecedented depth and have revealed vast cellular diversity among tumour cells and their niche. Anti-tumour immunity relies on cell-cell relationships within the tumour microenvironment1,2, yet many single-cell studies lack spatial context and rely on dissociated tissues3. Here we applied imaging mass cytometry to characterize the immunological landscape of 139 high-grade glioma and 46 brain metastasis tumours from patients. Single-cell analysis of more than 1.1 million cells across 389 high-dimensional histopathology images enabled the spatial resolution of immune lineages and activation states, revealing differences in immune landscapes between primary tumours and brain metastases from diverse solid cancers. These analyses revealed cellular neighbourhoods associated with survival in patients with glioblastoma, which we leveraged to identify a unique population of myeloperoxidase (MPO)-positive macrophages associated with long-term survival. Our findings provide insight into the biology of primary and metastatic brain tumours, reinforcing the value of integrating spatial resolution to single-cell datasets to dissect the microenvironmental contexture of cancer.
Asunto(s)
Neoplasias Encefálicas , Glioma , Análisis de la Célula Individual , Microambiente Tumoral , Humanos , Encéfalo/inmunología , Encéfalo/patología , Neoplasias Encefálicas/inmunología , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/secundario , Glioblastoma/inmunología , Glioblastoma/patología , Glioma/inmunología , Glioma/patología , Macrófagos/enzimología , Microambiente Tumoral/inmunología , Metástasis de la Neoplasia , Conjuntos de Datos como AsuntoRESUMEN
BACKGROUND: Depression literacy in general population constitutes an ability to understand depression, with knowledge of disease, its risk factors and symptoms. High levels of depression literacy promote early intervention, potentially reducing related disability. AIM: This study investigated the depression literacy in women visitors to clinics of a tertiary care hospital in Riyadh, Saudi Arabia. METHODS: Women of 18 and more years were surveyed during their visit to primary and other healthcare clinics of a public hospital in Riyadh. Knowledge on depression symptoms, causes and management approaches identified depression literate women scoring more than 30 points on a 42-item tool. RESULTS: Of the 409 participants, 65.5% were depression literate, 50% educated as college and above, 64.3% married, 50.7% housewives, 62.4% reported use of multiple information sources (range, 0-8) and had a mean age of 34.9 (standard deviation ( SD), 12.4) years. In a logistic regression model, participants scoring less than 30 for depression literacy were significantly associated with women having less than college-level education, divorced marital status and use of decreasing number of learning resources. CONCLUSION: Women with low education divorced; using fewer information sources need specific considerations by healthcare providers for assessment of depressive disorders in this setting.