The Glycolytic Pathway as a Target for Novel Onco-Immunology Therapies in Pancreatic Cancer

Pancreatic ductal adenocarcinoma (PDA) is one of the most lethal forms of human cancer, characterized by unrestrained progression, invasiveness and treatment resistance. To date, there are limited curative options, with surgical resection as the only effective strategy, hence the urgent need to discover novel therapies. A platform of onco-immunology targets is represented by molecules that play a role in the reprogrammed cellular metabolism as one hallmark of cancer. Due to the hypoxic tumor microenvironment (TME), PDA cells display an altered glucose metabolism—resulting in its increased uptake—and a higher glycolytic rate, which leads to lactate accumulation and them acting as fuel for cancer cells. The consequent acidification of the TME results in immunosuppression, which impairs the antitumor immunity. This review analyzes the genetic background and the emerging glycolytic enzymes that are involved in tumor progression, development and metastasis, and how this represents feasible therapeutic targets to counteract PDA. In particular, as the overexpressed or mutated glycolytic enzymes stimulate both humoral and cellular immune responses, we will discuss their possible exploitation as immunological targets in anti-PDA therapeutic strategies

SARS-CoV-2 Catalonia contact tracing program : evaluation of key performance indicators

Background: Guidance on SARS-CoV-2 contact tracing indicators have been recently revised by international public health agencies. The aim of the study is to describe and analyse contact tracing indicators based on Catalonia's (Spain) real data and proposing to update them according to recommendations. Methods: Retrospective cohort analysis including Catalonia's contact tracing dataset from 20 May until 31 December 2020. Descriptive statistics are performed including sociodemographic stratification by age, and differences are assessed over the study period. Results: We analysed 923,072 contacts from 301,522 SARS-CoV-2 cases with identified contacts (67.1% contact tracing coverage). The average number of contacts per case was 4.6 (median 3, range 1-243). A total of 403,377 contacts accepted follow-up through three phone calls over a 14-day quarantine period (84.5% of contacts requiring follow-up). The percentage of new cases declared as contacts 14 days prior to diagnosis evolved from 33.9% in May to 57.9% in November. All indicators significantly improved towards the target over time (p < 0.05 for all four indicators). Conclusions: Catalonia's SARS-CoV-2 contact tracing indicators improved over time despite challenging context. The critical revision of the indicator's framework aims to provide essential information in control policies, new indicators proposed will improve system delay's follow-up. The study provides information on COVID-19 indicators framework experience from country's real data, allowing to improve monitoring tools in 2021-2022. With the SARS-CoV-2 pandemic being so harmful to health systems and globally, is important to analyse and share contact tracing data with the scientific community

A tool for the automatic derivation of symbolic ode from symmetric net models

High-level Petri nets (HLPNs) are an expressive formalism well supported by a number of tools that automate the editing and the interactive simulation of models and some kinds of analytical techniques, mainly based on state-space exploration. Structural analysis of HLPNs is, however, a challenging task not yet adequately supported and it is often accomplished via the unfolding of an HLPN into a corresponding low-level Petri Net. An approach to derive a system of Ordinary Differential Equations (ODEs) from a Stochastic Symmetric Net (SSN) has been proposed a few years ago, based on the net's unfolding and subsequent grouping of similar equations. This method has been recently improved by providing an algorithm that directly derives a compact ODE system (from a partially unfolded net) in a symbolic way, through algebraic manipulation of SSN annotations. In this paper, we present the automation of the calculus of Symbolic ODEs (SODEs) for SSN models as a new module of SNexpression, a tool for the symbolic structural analysis of Symmetric Nets. An application of the tool/technique to a variant of a SIRS epidemic model including antibiotic resistance is also described

In pancreatic cancer chemotherapy increases anti-tumor responses to tumor associated antigens and potentiates DNA vaccination

Background Pancreatic ductal adenocarcinoma (PDA) is an almost incurable tumor that is mostly resistant to chemotherapy (CT). Adaptive immune responses to tumor-associated antigens (TAA) have been reported, but immunotherapy (IT) clinical trials have not yet achieved any significant increase in survival, confirming the suppressive environment of PDA. As CT has immune-modulating properties, we investigated the effect of gemcitabine (GEM) in antitumor effector responses to TAA in patients with PDA.Methods The IgG antibody repertoire in patients with PDA before and after CT was profiled by serological proteome analysis and ELISA and their ability to activate complement-dependent cytotoxicity (CDC) was measured. Peripheral T cells were stimulated in vitro with recombinant TAA, and specific proliferation, IFN-γ/IL-10 and CD8+/Treg ratios were measured. Mice that spontaneously developed PDA were treated with GEM and inoculated with an ENO1 (α−Enolase) DNA vaccine. In some experimental groups, the effect of depleting CD4, CD8 and B cells by specific antibodies was also evaluated.Results CT increased the number of TAA recognized by IgG and their ability to activate CDC. Evaluation of the IFN-γ/IL-10 ratio and CD8+/Treg ratios revealed that CT treatment shifted T cell responses to ENO1, G3P (glyceraldheyde-3-phosphate dehydrogenase), K2C8 (keratin, type II cytoskeletal 8) and FUBP1 (far upstream binding protein 1), four of the most recognized TAA, from regulatory to effector. In PDA mice models, treatment with GEM prior to ENO1 DNA vaccination unleashed CD4 antitumor activity and strongly impaired tumor progression compared with mice that were vaccinated or GEM-treated alone.Conclusions Overall, these data indicate that, in PDA, CT enhances immune responses to TAA and renders them suitable targets for IT

Behavior of hospitalized severe influenza cases according to the outcome variable in Catalonia, Spain, during the 2017-2018 season

Altres ajuts: Programme of Prevention, Surveillance and Control of Transmissible Diseases (PREVICET); CIBER de Epidemiología y Salud Pública (CIBERESP).Influenza is an important cause of severe illness and death among patients with underlying medical conditions and in the elderly. The aim of this study was to investigate factors associated with ICU admission and death in patients hospitalized with severe laboratory-confirmed influenza during the 2017-2018 season in Catalonia. An observational epidemiological case-to-case study was carried out. Reported cases of severe laboratory-confirmed influenza requiring hospitalization in 2017-2018 influenza season were included. Mixed-effects regression analysis was used to estimate the factors associated with ICU admission and death. A total of 1306 cases of hospitalized severe influenza cases were included, of whom 175 (13.4%) died and 217 (16.6%) were ICU admitted. Age 65-74 years and ≥ 75 years and having ≥ 2 comorbidities were positively associated with death (aOR 3.19; 95%CI 1.19-8.50, aOR 6.95, 95%CI 2.76-1.80 and aOR 1.99; 95%CI 1.12-3.52, respectively). Neuraminidase inhibitor treatment and pneumonia were negatively associated with death. The 65-74 years and ≥ 75 years age groups were negatively associated with ICU admission (aOR 0.41; 95%CI 0.23-0.74 and aOR 0.30; 95%CI 0.17-0.53, respectively). A factor positively associated with ICU admission was neuraminidase inhibitor treatment. Our results support the need to investigate the worst outcomes of hospitalized severe cases, distinguishing between death and ICU admission