Tumor immune contexture is a determinant of anti-CD19 CAR T cell efficacy in large B cell lymphoma.

Axicabtagene ciloleucel (axi-cel) is an anti-CD19 chimeric antigen receptor (CAR) T cell therapy approved for relapsed/refractory large B cell lymphoma (LBCL) and has treatment with similar efficacy across conventional LBCL subtypes. Toward patient stratification, we assessed whether tumor immune contexture influenced clinical outcomes after axi-cel. We evaluated the tumor microenvironment (TME) of 135 pre-treatment and post-treatment tumor biopsies taken from 51 patients in the ZUMA-1 phase 2 trial. We uncovered dynamic patterns that occurred within 2 weeks after axi-cel. The biological associations among Immunoscore (quantification of tumor-infiltrating T cell density), Immunosign 21 (expression of pre-defined immune gene panel) and cell subsets were validated in three independent LBCL datasets. In the ZUMA-1 trial samples, clinical response and overall survival were associated with pre-treatment immune contexture as characterized by Immunoscore and Immunosign 21. Circulating CAR T cell levels were associated with post-treatment TME T cell exhaustion. TME enriched for chemokines (CCL5 and CCL22), γ-chain receptor cytokines (IL-15, IL-7 and IL-21) and interferon-regulated molecules were associated with T cell infiltration and markers of activity. Finally, high density of regulatory T cells in pre-treatment TME associated with reduced axi-cel-related neurologic toxicity. These findings advance the understanding of LBCL TME characteristics associated with clinical responses to anti-CD19 CAR T cell therapy and could foster biomarker development and treatment optimization for patients with LBCL.

National survey and molecular diagnosis of Echinococcus granulosus sensu lato in livestock in France, 2012.

The parasitic species of the Echinococcus granulosus sensu lato (sl) complex are the causative agents of cystic echinococcosis in humans. The lifecycle of E. granulosus sl is essentially domestic, and is based on the consumption by dogs of hydatid cysts in viscera of livestock species. The aim of this study was to survey E. granulosus sensu lato in livestock in France. A 1-year national survey of E. granulosus sl in livestock at the slaughterhouse was organized in 2012 in France, with systematic molecular confirmation. The prevalence of E. granulosus ss nationally was 0.002% in sheep, mainly focused in the Alpine area, and 0.001% in cattle, with the distribution of cases throughout the country. Echinococcus canadensis G6/7 was observed only in Corsica in pigs, with a prevalence of nearly 1% in the island. A national prevalence of 0.0002% was estimated for E. ortleppi in cattle, due to seven cases distributed in two foci. The results of this survey are of particular interest because of the zoonotic risk associated with the presence of these parasite species, for which systematic control at the slaughterhouse should enable their elimination.

Building a molecular Listeria monocytogenes database to centralize and share PFGE typing data from food, environmental and animal strains throughout Europe.

The European Union Reference Laboratory (EURL) for Listeria monocytogenes (Lm) collaborates with a network of 35 National Reference Laboratories (NRLs) throughout Europe. Most of these NRLs are in charge of detecting and typing Lm strains from food, environment and animals, which are isolated nationally. The past few years EURL activities have enabled NRLs to reinforce typing capabilities according to standardised protocols. Consequently the need to exchange typing data within the NRL network has emerged. That is why the EURL has recently set up a EURL Lm Database (EURL Lm DB). Each NRL contributes data, which is then shared within the network. Data include strain-typing-results (PFGE and serotyping) and epidemiological information on the strains. This article describes (1) the EURL typing activities that led to the creation of the EURL Lm DB, (2) the different steps involved in developing the EURL Lm DB, and (3) the usefulness of this database for public health. The combined use of this database, with databases on human strains, is being integrated into the European surveillance system of Lm strains circulating throughout Europe. It should improve the detection of this pathogen and provide support for outbreak investigations.

Use of quantitative microbial risk assessment when investigating foodborne illness outbreaks: the example of a monophasic Salmonella Typhimurium 4,5,12:i:- outbreak implicating beef burgers.

A major community outbreak of salmonellosis occurred in France in October 2010. Classical epidemiological investigations led to the identification of beef burgers as the cause of the outbreak and the presence of the emerging monophasic Salmonella Typhimurium 4,5,12:i:-. The objective of this study was to understand the events that led to this large outbreak, that is to say, what are the contributing factors associated with consumer exposure to Salmonella. To this end, intensive microbiological investigations on several beef burgers were conducted and a risk assessment model was built. The microbiological results confirm the presence of Salmonella in all analysed frozen burgers at high levels of contamination above 1000 MPN/g. These results in frozen burgers combined with a model of thermal destruction were used to estimate the dose ingested by the exposed persons. Most people that consumed cooked beef burgers were exposed from 1.6 to 3.1 log10 (MPN). The number of sick people predicted with a dose-response relationship for Salmonella is consistent with the observed number of salmonellosis cases. The very high initial contamination level in frozen beef burgers is the primary cause of this large outbreak rather than bad cooking practices. Intensive investigations, modelling of the initial contamination and quantitative exposure and risk assessments are complementary to epidemiological investigation. They can be valuable elements for the assessment of missing information or the identification of the primary causes of outbreaks.

Human infections due to Salmonella Napoli: a multicountry, emerging enigma recognized by the Enter-net international surveillance network.

Human infections caused by Salmonella enterica serovar Napoli are relatively uncommon in Europe. Napoli was ranked 22nd in the Enter-net Salmonella database for 2006 with 295 cases (0.28%) of the 105,635 from 29 European countries. For the 18 countries that provided data for all the years 2000-2006, the number of cases rose from 122 out of 116,915 (0.10%) in 2000 to 293 out of 80,318 (0.36%) in 2006-an increase of 140.2%. Over 87% of cases came from three countries, France, Italy, and Switzerland. The epidemiology of the human cases showed an increased frequency in those aged under 5 or over 64, and both sexes were equally represented. Napoli isolates were also reported from nonhuman sources, mainly environmental samples and poultry. Strains compared by pulsed-field gel electrophoresis exhibited high levels of diversity between human, animal, and environmental sources. No single factor has been recognized as causing this rise, hence no public health interventions can be made or advice given to ensure that it does not persist. A 140% rise in 7 years indicates that the public health problem will continue, and further multidisciplinary investigations are needed to solve this enigma.