Identification of a class of non-conventional ER-stress-response-derived immunogenic peptides

Efforts to overcome resistance to immune checkpoint blockade therapy have focused on vaccination strategies using neoepitopes, although they cannot be applied on a large scale due to the “private” nature of cancer mutations. Here, we show that infection of tumor cells with Salmonella induces the opening of membrane hemichannels and the extracellular release of proteasome-generated peptides by the exacerbation of endoplasmic reticulum (ER) stress. Peptides released by cancer cells foster an antitumor response in vivo, both in mice bearing B16F10 melanomas and in dogs suffering from osteosarcoma. Mass spectrometry analysis on the supernatant of human melanoma cells revealed 12 peptides capable of priming healthy-donor CD8+ T cells that recognize and kill human melanoma cells in vitro and when xenotransplanted in vivo. Hence, we identified a class of shared tumor antigens that are generated in ER-stressed cells, such as tumor cells, that do not induce tolerance and are not presented by healthy cells

Identification of a class of non-conventional ER-stress-response-derived immunogenic peptides

Efforts to overcome resistance to immune checkpoint blockade therapy have focused on vaccination strategies using neoepitopes, although they cannot be applied on a large scale due to the “private” nature of cancer mutations. Here, we show that infection of tumor cells with Salmonella induces the opening of membrane hemichannels and the extracellular release of proteasome-generated peptides by the exacerbation of endoplasmic reticulum (ER) stress. Peptides released by cancer cells foster an antitumor response in vivo, both in mice bearing B16F10 melanomas and in dogs suffering from osteosarcoma. Mass spectrometry analysis on the supernatant of human melanoma cells revealed 12 peptides capable of priming healthy-donor CD8+ T cells that recognize and kill human melanoma cells in vitro and when xenotransplanted in vivo. Hence, we identified a class of shared tumor antigens that are generated in ER-stressed cells, such as tumor cells, that do not induce tolerance and are not presented by healthy cells

A Target Animal Effectiveness Study on Adjuvant Peptide-Based Vaccination in Dogs with Non-Metastatic Appendicular Osteosarcoma Undergoing Amputation and Chemotherapy

Despite efforts to develop novel treatment strategies, human and canine osteosarcomas continue to have poor prognosis and limited overall survival. The aim of this clinical trial was to test the antitumor effect and safety of multiple dermal administrations of a peptide-based anticancer vaccine in dogs with non-metastatic appendicular osteosarcoma undergoing standard of care (SOC), consisting of limb amputation and adjuvant chemotherapy. Salmonella-infected canine osteosarcoma cells were induced to release immunogenic peptides in the extracellular space via Cx43 hemichannels opening; the secretome was collected and constituted the vaccine. Dogs with non-metastatic appendicular osteosarcoma were eligible for recruitment. Following limb amputation and adjuvant carboplatin, dogs were vaccinated on a monthly basis for six times and followed up with serial thoracic radiographs. A population of dogs undergoing SOC treatment (amputation and adjuvant carboplatin) before the vaccine was available served as controls. Primary endpoints were time to metastasis (TTM) and tumor-specific survival (TSS). Secondary endpoints were feasibility, toxicity, T-cell and humoral immune responses. A total of 20 dogs were vaccinated along with SOC and 34 received SOC only. Vaccine-specific humoral and T-cell responses were observed; their amplitude correlated with TSS. Vaccine-associated toxicity was not recorded. TTM and TSS were significantly longer in vaccinated versus unvaccinated dogs (TTM: 308 vs. 240 days, respectively; p = 0.010; TSS: 621 vs. 278 days, respectively; p = 0.002). In dogs with non-metastatic osteosarcoma undergoing SOC, the addition of a bacteria-based vaccination strategy increased TTM, thereby prolonging survival, while maintaining a safe profile. Additionally, vaccinated dogs developed a long-term tumor-specific response, as documented by the immunomonitoring of these patients over time. These results hold promise for future management of canine osteosarcoma

In-Memory Principal Component Analysis by Crosspoint Array of Resistive Switching Memory: A New Hardware Approach for Energy-Efficient Data Analysis in Edge Computing

open8siopenMannocci Piergiulio; Baroni Andrea; Melacarne Enrico; Zambelli Cristian; Olivo Piero; Perez Eduardo; Wenger Christian; Ielmini DanieleMannocci, Piergiulio; Baroni, Andrea; Melacarne, Enrico; Zambelli, Cristian; Olivo, Piero; Perez, Eduardo; Wenger, Christian; Ielmini, Daniel

Data from a three-wave complete longitudinal design survey on career calling and related constructs

This dataset provides de-identified raw responses to a non-anonymous three-wave online survey with a 12-month time lag. Data collection was part of a larger project on the development of career calling in Italian college students. The first wave was collected during the fall of 2014. Participants were bachelor's or master's students enrolled in 24 different study domains and 4 different universities. Sample sizes for each wave are NT1 = 5,886, NT2 = 1,700 and NT3 = 881, 434 participants provided valid responses at all the three waves. Consent form was electronic. Dataset and codebook can be found here: https://osf.io/v56du/. The sample is mainly composed of women (63.8%, at Time 1). Participants' mean age at Time 1 was 23.37 years (SD = 5.39). The survey was in Italian and included multiple-item measures of career calling, intrinsic and extrinsic motivation, social support, engaged learning, clarity of professional identity, and quality of mentorship. Socio-demographic information and academic performance indicators are provided. The dataset is necessary to reproduce previously published results (Vianello et al., 2018) and can be useful to 1) investigate cross-cultural differences between college students from Italy and other countries; 2) investigate person-level variability in predictors and consequences of change in the variables collected over time; 3) develop and/or validate new statistical models for longitudinal data; and 4) develop and/or test original theoretical hypotheses

The Theory and Practices of Evaluating Transformative Learning Processes

This paper aims at defining a framework for the most recent approaches and tools used to evaluate Transformative Learning process and its outcomes. Actually, many experiences and tools have been discussed and validated in the international debate. The literature shows that there are different approaches to validate and use these tools suggesting that the Transformative Learning Theory is interpreted in many ways. This chapter provides a critical analysis of the European and American approaches and tools used to evaluate TL processes. The objectives of the paper are: 1) showing the state of the art of assessment perspectives in TLT; 2) defining a framework to categorize them; 3) depict a possible evolution of TL assessment approaches