Decoding the secret of extracellular vesicles in the immune tumor microenvironment of the glioblastoma: on the border of kingdoms.

Over the last decades, extracellular vesicles (EVs) have become increasingly popular for their roles in various pathologies, including cancer and neurological and immunological disorders. EVs have been considered for a long time as a means for normal cells to get rid of molecules it no longer needs. It is now well established that EVs play their biological roles also following uptake or by the interaction of EV surface proteins with cellular receptors and membranes. In this review, we summarize the current status of EV production and secretion in glioblastoma, the most aggressive type of glioma associated with high mortality. The main purpose is to shed light on the EVs as a universal mediator of interkingdom and intrakingdom communication in the context of tumor microenvironment heterogeneity. We focus on the immunomodulatory EV functions in glioblastoma-immune cross-talk to enhance immune escape and reprogram tumor-infiltrating immune cells. We critically examine the evidence that GBM-, immune cell-, and microbiome-derived EVs impact local tumor microenvironment and host immune responses, and can enter the circulatory system to disseminate and drive premetastatic niche formation in distant organs. Taking into account the current state of the art in intratumoral microbiome studies, we discuss the emerging role of bacterial EV in glioblastoma and its response to current and future therapies including immunotherapies.

CAR T-cells for colorectal cancer immunotherapy: Ready to go?

Chimeric antigen receptor (CAR) T-cells represent a new genetically engineered cell-based immunotherapy tool against cancer. The use of CAR T-cells has revolutionized the therapeutic approach for hematological malignancies. Unfortunately, there is a long way to go before this treatment can be developed for solid tumors, including colorectal cancer. CAR T-cell therapy for colorectal cancer is still in its early stages, and clinical data are scarce. Major limitations of this therapy include high toxicity, relapses, and an impermeable tumor microenvironment for CAR T-cell therapy in colorectal cancer. In this review, we summarize current knowledge, highlight challenges, and discuss perspectives regarding CAR T-cell therapy in colorectal cancer.

Predictors of Severity in Covid-19 Patients in Casablanca, Morocco.

Background Morocco was affected, as were other countries, by the coronavirus disease 2019 (COVID-19) pandemic. Many risk factors of COVID-19 severity have been described, but data on infected patients in North Africa are limited. We aimed to explore the predictive factors of disease severity in COVID-19 patients in a tertiary hospital in Casablanca. Methods In this single-center, retrospective, observational study, we included all adult patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, admitted to Sheikh Khalifa International University Hospital in Casablanca between March 18 and May 20, 2020. Patients were separated into two groups: Non-severe patients were those with mild or moderate forms of COVID-19, and severe patients were those admitted to the intensive care unit (ICU) who had one of the following signs-respiratory rate > 30 breaths/min; oxygen saturation < 93% on room air; acute respiratory distress syndrome (ARDS); or required mechanical ventilation. Demographic, clinical, laboratory data, and outcomes were reviewed. We used univariable and multivariable logistic regression to explore predictive factors of severity. Results We reported 134 patients with confirmed SARS-CoV-2 infection. The median age was 53 years (interquartile range [IQR], 36-64), and 73 (54.5%) were men. Eighty-nine non-severe patients (66.4%) were admitted to single bedrooms, and 45 (33.6%) were placed in the ICU. The median time from illness onset to hospital admission was seven days (IQR, 3.0-7.2). Ninety-nine patients (74%) were admitted directly to the hospital, and 35 (26%) were transferred from other structures. Also, 68 patients (65.4%) were infected in clusters. Of the 134 patients, 61 (45.5%) had comorbidities, such as hypertension (n = 36; 26.9%), diabetes (n = 19; 14.2%), and coronary heart disease (n = 16; 11.9%). The most frequent symptoms were fever (n = 61; 45.5%), dry cough (n = 59; 44%), and dyspnea (n = 39; 29%). A total of 127 patients received hydroxychloroquine and azithromycin (95%). Eleven critical cases received lopinavir/ritonavir (8.2%). Five patients received tocilizumab (3.7%). We reported 13 ARDS cases in ICU patients (29%), eight with acute kidney injury (17.8%), and four thromboembolic events (8.8%). Fourteen ICU patients (31.1%) died at 28 days. In univariable analysis, older men with one or more comorbidities, infection in a cluster, chest scan with the COVID-19 Reporting and Data System (CO-RADS) 5, lymphopenia, high rates of ferritin, C-reactive protein (CRP), D-dimer, and lactate dehydrogenase were associated with severe forms of COVID-19. Multivariable logistic regression model founded increasing odds of severity associated with older age (odds ratio [OR] 1.05, 95% confidence interval [CI] 1.01-1.09, P = .0039), men (OR 3.19, CI 1.06-9.60, P = .016), one or more comorbidities (OR 4.36, CI 1.32-14.45, P = .016), CRP > 10 mg/L (OR 5.47, CI 1.57-19.10, P = .008), and lymphopenia lower than 0.8 x109/L (OR 6.65, CI 1.43-30.92, P = .016). Conclusions Clinicians should consider older male patients with comorbidities, lymphopenia, and a high CRP rate as factors to predict severe forms of COVID-19 earlier. The higher severity of infected patients in clusters must be confirmed by epidemiological and genetic studies.