Biomarkers guiding the neoadjuvant use of immune checkpoint inhibitors (ICBs) are needed for patients with localized muscle invasive bladder cancers (MIBC). Profiling tumor and blood samples, we found that follicular helper CD4+ T cells (TFH) are among the best therapeutic targets of pembrolizumab correlating with progression-free survival. TFH were associated with tumoral CD8 and PD-L1 expression at baseline, and the induction of tertiary lymphoid structures post-pembrolizumab. Blood central memory TFH accumulated in tumors where they produce CXCL13, a chemokine found in the plasma of responders only. IgG4+CD38+ TFH residing in bladder tissues correlated with clinical benefit. Finally, TFH and IgG directed against urothelium invasive Escherichia coli dictated clinical responses to pembrolizumab in three independent cohorts. The links between tumor infection and success of ICB immunomodulation should be prospectively assessed at a larger scale.

Background: More than 1 year after the beginning of the international spread of coronavirus 2019 (COVID-19), the reasons explaining its apparently lower reported burden in Africa are still to be fully elucidated. Few studies previously investigated the potential reasons explaining this epidemiological observation using data at the level of a few African countries. However, an updated analysis considering the various epidemiological waves and variables across an array of categories, with a focus on African countries might help to better understand the COVID-19 pandemic on the continent. Thus, we investigated the potential reasons for the persistently lower transmission and mortality rates of COVID-19 in Africa.Methods: Data were collected from publicly available and well-known online sources. The cumulative numbers of COVID-19 cases and deaths per 1 million population reported by the African countries up to February 2021 were used to estimate the transmission and mortality rates of COVID-19, respectively. The covariates were collected across several data sources: clinical/diseases data, health system performance, demographic parameters, economic indicators, climatic, pollution, and radiation variables, and use of social media. The collinearities were corrected using variance inflation factor (VIF) and selected variables were fitted to a multiple regression model using the R statistical package.Results: Our model (adjusted R-squared: 0.7) found that the number of COVID-19 tests per 1 million population, GINI index, global health security (GHS) index, and mean body mass index (BMI) were significantly associated (P < 0.05) with COVID-19 cases per 1 million population. No association was found between the median life expectancy, the proportion of the rural population, and Bacillus Calmette–Guérin (BCG) coverage rate. On the other hand, diabetes prevalence, number of nurses, and GHS index were found to be significantly associated with COVID-19 deaths per 1 million population (adjusted R-squared of 0.5). Moreover, the median life expectancy and lower respiratory infections rate showed a trend towards significance. No association was found with the BCG coverage or communicable disease burden.Conclusions: Low health system capacity, together with some clinical and socio-economic factors were the predictors of the reported burden of COVID-19 in Africa. Our results emphasize the need for Africa to strengthen its overall health system capacity to efficiently detect and respond to public health crises.

Culturomics, a high throughput culture method with rapid identification of the colonies by Matrix Assisted Laser Desorption Ionization/Time Of Flight Mass Spectrometry (MALDI-TOF MS), has demonstrated its contribution to the exploration of the gut microbiota over the past 10 years. However, the cost, work time and workload, considerably limit its use on a large scale or emergency context. Here, by testing two different stool samples, including a stool sample from a patient requiring rapid immunotherapy treatment, we tested a new fast culturomic protocol using two pre-incubation media, blood culture bottle and YCFA modified medium. Both media were supplemented with 2 ml of rumen fluid filtered at 0.2 μm and 2 ml of defibrinated and sterile sheep blood. Unlike the standard culturomics, subculturing of blood culture bottle were performed at reduced incubation time (3 h, 6 h, 9 h, 24 h) and at a longer incubation time (3 days, 7 days, and 10 days) at 37°C. By testing 5,200 colonies per MALDI-TOF MS and obtaining a comparable number of cultured bacterial species (131 to 143) in a stool sample, this new protocol reduced the number of colonies tested by 57%, working time by 78.6% and cost by 72.2%. In addition, we highlighted that the proportion of strict anaerobic species has increased by 24%, known to be the preferential targets for biotherapy, including Faecalibacterium prausnitzii, Akkermansia muciniphila, Christensenella minuta, and Phascolarctobacterium faecium. Finally, this work showed that some bacterial species grew earlier but disappeared with prolonged incubation times.