Tissue-resident memory T cells (Trm) represent a new subset of long-lived memory T cells that remain in tissue and do not recirculate. Although they are considered as early immune effectors in infectious diseases, their role in cancer immunosurveillance remains unknown. In a preclinical model of head and neck cancer, we show that intranasal vaccination with a mucosal vector, the B subunit of Shiga toxin, induces local Trm and inhibits tumour growth. As Trm do not recirculate, we demonstrate their crucial role in the efficacy of cancer vaccine with parabiosis experiments. Blockade of TFGβ decreases the induction of Trm after mucosal vaccine immunization, resulting in the lower efficacy of cancer vaccine. In order to extrapolate this role of Trm in humans, we show that the number of Trm correlates with a better overall survival in lung cancer in multivariate analysis. The induction of Trm may represent a new surrogate biomarker for the efficacy of cancer vaccine. This study also argues for the development of vaccine strategies designed to elicit them.

Several medications commonly used for a number of medical conditions share a property of functional inhibition of acid sphingomyelinase (ASM), or FIASMA. Preclinical and clinical evidence suggest that the (ASM)/ceramide system may be central to SARS‐CoV‐2 infection. We examined the potential usefulness of FIASMA use among patients hospitalized for severe COVID‐19 in an observational multicenter study conducted at Greater Paris University hospitals. Of 2,846 adult patients hospitalized for severe COVID‐19, 277 (9.7%) were taking a FIASMA medication at the time of their hospital admission. The primary endpoint was a composite of intubation and/or death. We compared this endpoint between patients taking vs. not taking a FIASMA medication in time‐to‐event analyses adjusted for sociodemographic characteristics and medical comorbidities. The primary analysis was a Cox regression model with inverse probability weighting (IPW). Over a mean follow‐up of 9.2 days (SD=12.5), the primary endpoint occurred in 104 patients (37.5%) receiving a FIASMA medication, and 1,060 patients (41.4%) who did not. Despite being significantly and substantially associated with older age and greater medical severity, FIASMA medication use was significantly associated with reduced likelihood of intubation or death in both crude (HR=0.71; 95%CI=0.58‐0.87; p<0.001) and primary IPW (HR=0.58; 95%CI=0.46‐0.72; p<0.001) analyses. This association remained significant in multiple sensitivity analyses and was not specific to one particular FIASMA class or medication. These results show the potential importance of the ASM/ceramide system in COVID‐19 and support the continuation of FIASMA medications in these patients. Double‐blind controlled randomized clinical trials of these medications for COVID‐19 are needed.

A survey conducted after 6 months of use at the Necker Children's Hospital shows a high rate of satisfaction among the users (96.6%). During this period, 122 users performed 2837 queries, accessed 4,267 patients' records and included 36,632 patients in 131 cohorts. The source code is available at this github link https://github.com/imagine-bdd/DRWH. A demonstration based on PubMed abstracts is available at https://imagine-plateforme-bdd.fr/dwh_pubmed/.

Background Coronavirus disease‐2019 (COVID‐19) has been associated with cardiovascular complications and coagulation disorders. Objectives To explore the coagulopathy and endothelial dysfunction in COVID‐19 patients. Methods The study analyzed clinical and biological profiles of patients with suspected COVID‐19 infection at admission, including hemostasis tests and quantification of circulating endothelial cells (CECs). Results Among 96 consecutive COVID‐19‐suspected patients fulfilling criteria for hospitalization, 66 were tested positive for SARS‐CoV‐2. COVID‐19‐positive patients were more likely to present with fever (P = .02), cough (P = .03), and pneumonia at computed tomography (CT) scan (P = .002) at admission. Prevalence of D‐dimer >500 ng/mL was higher in COVID‐19‐positive patients (74.2% versus 43.3%; P = .007). No sign of disseminated intravascular coagulation were identified. Adding D‐dimers >500 ng/mL to gender and pneumonia at CT scan in receiver operating characteristic curve analysis significantly increased area under the curve for COVID‐19 diagnosis. COVID‐19‐positive patients had significantly more CECs at admission (P = .008) than COVID‐19‐negative ones. COVID‐19‐positive patients treated with curative anticoagulant prior to admission had fewer CECs (P = .02) than those without. Interestingly, patients treated with curative anticoagulation and angiotensin‐converting‐enzyme inhibitors or angiotensin receptor blockers had even fewer CECs (P = .007). Conclusion Curative anticoagulation could prevent COVID‐19‐associated coagulopathy and endothelial lesion.

Objective: Preliminary data from different cohorts of small sample size or with short follow-up indicate poorer prognosis in people with obesity compared with other patients. This study aims to precisely describe the strength of association between obesity in patients hospitalized with coronavirus disease 2019 (COVID-19) and mortality and to clarify the risk according to usual cardiometabolic risk factors in a large cohort. Methods: This is a prospective cohort study including 5,795 patients aged 18 to 79 years hospitalized from February 1 to April 30, 2020, in the Paris area, with confirmed infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Adjusted regression models were used to estimate the odds ratios (ORs) and 95% CIs for the mortality rate at 30 days across BMI classes, without and with imputation for missing BMI values. Results: Eight hundred ninety-one deaths had occurred at 30 days. Mortality was significantly raised in people with obesity, with the following ORs for BMI of 30 to 35 kg/m 2 , 35 to 40 kg/m 2 , and >40 kg/m 2 : 1.89 (95% CI: 1.45-2.47), 2.79 (95% CI: 1.95-3.97), and 2.55 (95% CI: 1.62-3.95), respectively (18.5-25 kg/m 2 was used as the reference class). This increase holds for all age classes. Conclusions: Obesity doubles mortality in patients hospitalized with COVID-19.

The rise of personalized medicine and the availability of high-throughput molecular analyses in the context of clinical care have increased the need for adequate tools for translational researchers to manage and explore these data. We reviewed the biomedical literature for translational platforms allowing the management and exploration of clinical and omics data, and identified seven platforms: BRISK, caTRIP, cBio Cancer Portal, G-DOC, iCOD, iDASH and tranSMART. We analyzed these platforms along seven major axes. (1) The community axis regrouped information regarding initiators and funders of the project, as well as availability status and references. (2) We regrouped under the information content axis the nature of the clinical and omics data handled by each system. (3) The privacy management environment axis encompassed functionalities allowing control over data privacy. (4) In the analysis support axis, we detailed the analytical and statistical tools provided by the platforms. We also explored (5) interoperability support and (6) system requirements. The final axis (7) platform support listed the availability of documentation and installation procedures. A large heterogeneity was observed in regard to the capability to manage phenotype information in addition to omics data, their security and interoperability features. The analytical and visualization features strongly depend on the considered platform. Similarly, the availability of the systems is variable. This review aims at providing the reader with the background to choose the platform best suited to their needs. To conclude, we discuss the desiderata for optimal translational research platforms, in terms of privacy, interoperability and technical features.

We aimed to determine whether pretherapeutic assessment of HPV circulating tumoral DNA (HPV ctDNA) by droplet‐based digital PCR (ddPCR) could constitute a predictive and prognostic biomarker for HPV‐associated oropharyngeal squamous cell carcinoma (OPSCC). A mono‐institutional prospective biomarker study on 66 patients with p16+/HPV16‐positive oropharyngeal squamous cell carcinoma (OPSCC) was conducted in European Georges Pompidou Hospital, Paris, France. Blood samples were collected at the time of diagnosis before any treatment. Optimized digital PCR assays were used to quantify HPV16 ctDNA. Forty‐seven (71%) patients showed a positive pretherapeutic HPV ctDNA at time of diagnosis. Interestingly, the quantity of HPV16 ctDNA at baseline, as assessed by ddPCR, was significantly correlated with the T/N/M status or OPSCC stages according to the 2018 new staging criteria for high‐risk human papillomavirus (HR HPV) related OPSCC from American Joint Committee on Cancer (AJCC). Moreover, all recurrences and the majority (83%) of death reported events occurred in patients with positive HPV16 ctDNA at baseline. Finally, when posttreatment blood samples were available (n = 6), the kinetic of pretreatment/posttreatment HPV16 ctDNA was clearly associated with treatment success or failure. HPV ctDNA monitoring by ddPCR could constitute a useful and noninvasive dynamic biomarker to select HR HPV‐related OPSCC patients eligible for potential treatment de‐escalation and to monitor treatment response.

Introduction: Multiple nodules in the lung are being diagnosed with an increasing frequency thanks to high-quality computed tomography imaging. In patients with lung cancer, this situation represents up to 10% of patients who have an operation. For clinical management, it is important to classify the disease as intrapulmonary metastasis or multiple primary lung carcinoma to define TNM classification and optimize therapeutic options. In the present study, we evaluated the respective and combined input of histological and molecular classification to propose a classification algorithm for multiple nodules.