Rethinking immunotherapy in meningiomas.
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ABSTRACT:
SUBMITTER: Terabe M
PROVIDER: S-EPMC8563318 | biostudies-literature | 2021 Nov
REPOSITORIES: biostudies-literature
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Project description:Meningiomas are common tumors that account for approximately one third of CNS tumors diagnosed every year. They are classified by the World Health Organization in grades I-III. Higher grades have an increased rate of growth, invasiveness, rate of recurrence, and worse outcomes than lower grades. Most meningiomas are grade I, while ~18% of meningiomas are grade II and III in hospital-based series. Meningiomas are typically "benign" tumors that are treated with surgery and radiation. However, when they recur or are unresectable, treatment options are very limited, especially since they are chemotherapy-resistant. Recent advances in the treatment of cancers with immunotherapy have focused on checkpoint blockade as well as other types of immunotherapy. There is emerging evidence supporting the use of immunotherapy as a potentially effective treatment strategy for meningioma patients. The immune microenvironment of meningiomas is a complex interplay of genetic alterations, immunomodulatory protein expression, and tumor-immune cell interactions. Meningiomas are known to be infiltrated by immune cells including microglia, macrophages, B-cells, and T-cells. Several mechanisms contribute to decreased an ti-tumor immune response, allowing tumor growth and evasion of the immune system. We discuss the most current knowledge on the immune micro-environment of meningiomas, preclinical findings of immunotherapy in meningiomas, meningioma immunotherapy clinical trials, and also offer insight into future prospects for immunotherapies in meningiomas.
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Project description:Studies of morbidity compression routinely report the average number of years spent in an unhealthy state but do not report variation in age at morbidity onset. Variation was highlighted by Fries (1980) as crucial for identifying disease postponement. Using incidence of first hospitalization after age 60, as one working example, we estimate variation in morbidity onset over a 27-year period in Denmark. Annual estimates of first hospitalization and the population at risk for 1987 to 2014 were identified using population-based registers. Sex-specific life tables were constructed, and the average age, the threshold age, and the coefficient of variation in age at first hospitalization were calculated. On average, first admissions lasting two or more days shifted towards older ages between 1987 and 2014. The average age at hospitalization increased from 67.8 years (95% CI 67.7-67.9) to 69.5 years (95% CI 69.4-69.6) in men, and 69.1 (95% CI 69.1-69.2) to 70.5 years (95% CI 70.4-70.6) in women. Variation in age at first admission increased slightly as the coefficient of variation increased from 9.1 (95% CI 9.0-9.1) to 9.9% (95% CI 9.8-10.0) among men, and from 10.3% (95% CI 10.2-10.4) to 10.6% (95% CI 10.5-10.6) among women. Our results suggest populations are ageing with better health today than in the past, but experience increasing diversity in healthy ageing. Pensions, social care, and health services will have to adapt to increasingly heterogeneous ageing populations, a phenomenon that average measures of morbidity do not capture.
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Project description:Lactobacillus helveticus is a rod-shaped lactic acid bacterium that is widely used in the manufacture of fermented dairy foods and for production of bioactive peptides from milk proteins. Although L. helveticus is commonly associated with milk environments, phylogenetic studies show it is closely related to an intestinal species, Lactobacillus acidophilus, which has been shown to impart probiotic health benefits to humans. This relationship has fueled a prevailing hypothesis that L. helveticus is a highly specialized derivative of L. acidophilus which has adapted to acidified whey. However, L. helveticus has also been sporadically recovered from non-dairy environments, which argues the species may not be as highly specialized as is widely believed. This study employed genome sequence analysis and comparative genome hybridizations to investigate genomic diversity among L. helveticus strains collected from cheese, whey, and whiskey malt, as well as commercial cultures used in manufacture of cheese or bioactive dairy foods. Results revealed considerable variability in gene content between some L. helveticus strains, and indicated the species should not be viewed as a strict dairy-niche specialist. In addition, comparative genomic analyses provided new insight on several industrially and ecologically important attributes of L. helveticus that may facilitate commercial strain selection.
2013-08-16 | GSE23660 | GEO
Project description:Although meningiomas are the most common tumor in the central nervous system, their incidence, epidemiology, and clinical outcomes have historically been poorly defined. This has been attributed to their benign course, difficulty obtaining histologic diagnosis, and lack of uniform database registration. Their clinical behavior can range from a silent incidentaloma to a lethal tumor. Projections of an aging population should raise medical awareness of an expectant rise in the incidence of meningiomas. This disease increases with advancing age, has a female predilection, and exposure to ionizing radiation is associated with a higher risk for disease development. There have been minimal advances in treatment, except in radiation therapy. Although no U.S. Food and Drug Administration-approved systemic therapy exists, there are treatment options that include hydroxyurea and sandostatin. Currently, no molecularly targeted therapy has provided clinical benefit, although recurring molecular alterations are present and novel therapies are being investigated.
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