TIMP1 Mediates Astrocyte-Dependent Local Immunosuppression in Brain Metastasis Acting on Infiltrating CD8+ T Cells.

Immunotherapies against brain metastases have shown clinical benefits when applied to asymptomatic patients, but they are largely ineffective in symptomatic cases for unknown reasons. Here, we dissect the heterogeneity in metastasis-associated astrocytes using single-cell RNA sequencing and report a population that blocks the antitumoral activity of infiltrating T cells. This protumoral activity is mediated by the secretion of tissue inhibitor of metalloproteinase-1 (TIMP1) from a cluster of pSTAT3+ astrocytes that acts on CD63+ CD8+ T cells to modulate their function.

[Geriatric syndromes in intermediate care resources: Screening, prevalence and inpatient mortality. Multicenter prospective study].

Objective: To determine the prevalence of geriatric syndromes (GS) in the geriatric population of the different intermediate care resources, as well as its relationship with intrahospital mortality.

Material And Methods: A prospective observational descriptive study, carried out in intermediate care resources in the Vic area (Barcelona) between July 2018 and September 2019. All people aged ≥65 years and/or criteria of complex chronic patient and/or advanced chronic disease, who were assessed for the presence of GS using the trigger questions of the Frail VIG-Index (IF-VIG), administered at baseline, on admission, on discharge and 30 days after discharge.

Protocol to generate murine organotypic brain cultures for drug screening and evaluation of anti-metastatic efficacy.

Organotypic brain cultures are short-term assays that phenotypically and functionally recapitulate brain metastatic cells in vivo. Here, we present a protocol to generate murine organotypic brain cultures for drug screening. We describe steps for sectioning of murine brains and plating of organotypic cultures.

Stratification of radiosensitive brain metastases based on an actionable S100A9/RAGE resistance mechanism.

Whole-brain radiotherapy (WBRT) is the treatment backbone for many patients with brain metastasis; however, its efficacy in preventing disease progression and the associated toxicity have questioned the clinical impact of this approach and emphasized the need for alternative treatments. Given the limited therapeutic options available for these patients and the poor understanding of the molecular mechanisms underlying the resistance of metastatic lesions to WBRT, we sought to uncover actionable targets and biomarkers that could help to refine patient selection. Through an unbiased analysis of experimental in vivo models of brain metastasis resistant to WBRT, we identified activation of the S100A9-RAGE-NF-κB-JunB pathway in brain metastases as a potential mediator of resistance in this organ.

Gene therapy in the management of oral cancer: review of the literature.

Gene therapy essentially consists of introducing specific genetic material into target cells without producing toxic effects on surrounding tissue. Advances over recent decades in the surgical, radiotherapeutic and chemotherapeutic treatment of oral cancer patients have not produced a significant improvement in patient survival. Increasing interest is being shown in developing novel therapies to reverse oral epithelial dysplastic lesions.