Multi-antigen Vaccination With Simultaneous Engagement of the OX40 Receptor Delays Malignant Mesothelioma Growth and Increases Survival in Animal Models

Malignant Mesothelioma (MM) is a rare and highly aggressive cancer that develops from mesothelial cells lining the pleura and other internal cavities, and is often associated with asbestos exposure. To date, no effective treatments have been made available for this pathology. Herein, we propose a novel immunotherapeutic approach based on a unique vaccine targeting a series of antigens that we found expressed in different MM tumors, but largely undetectable in normal tissues. This vaccine, that we term p-Tvax, is comprised of a series of immunogenic peptides presented by both MHC-I and -II to generate robust immune responses. The peptides were designed using in silico algorithms that discriminate between highly immunogenic T cell epitopes and other harmful epitopes, such as suppressive regulatory T cell epitopes and autoimmune epitopes. Vaccination of mice with p-Tvax led to antigen-specific immune responses that involved both CD8+ and CD4+ T cells, which exhibited cytolytic activity against MM cells in vitro. In mice carrying MM tumors, p-Tvax increased tumor infiltration of CD4+ T cells. Moreover, combining p-Tvax with an OX40 agonist led to decreased tumor growth and increased survival. Mice treated with this combination immunotherapy displayed higher numbers of tumor-infiltrating CD8+ and CD4+ T cells and reduced T regulatory cells in tumors. Collectively, these data suggest that the combination of p-Tvax with an OX40 agonist could be an effective strategy for MM treatment

Convergence in international business ethics? A comparative study of ethical philosophies, thinking style, and ethical decision-making between US and Korean managers

This study investigates the relationship among ethical philosophy, thinking style, and managerial ethical decision-making. Based on the premise that business ethics is a function of culture and time, we attempt to explore two important questions as to whether the national differences in managerial ethical philosophies remain over time and whether the relationship between thinking style and ethical decision-making is consistent across different national contexts. We conducted a survey on Korean managers’ ethical decision-making and thinking style and made a cross-cultural, cross-temporal comparison with the results presented by previous studies that surveyed Korean and US managers with the same questionnaire at different points in time. Our analysis revealed that Korean managers have become more reliant on rule utilitarianism for ethical decision-making over the last two decades, which is dominantly used by US managers, corroborating our convergence hypothesis built on social contracts theory. However, as opposed to previous research, we found that managers with a balanced linear and nonlinear thinking style do not necessarily make more ethical decisions compared to those with a predominantly linear or nonlinear thinking style. This study contributes to international business ethics literature by presenting a theoretical framework that may explain the convergence of ethical philosophies employed by managers in different national contexts over time, and that the relationship between thinking style and managerial ethical decision-making may not be universal, but contingent on contextual factors

Eyes wide open: perceived exploitation and its consequences

Drawing on the array of literature on exploitation from several social science disciplines, we propose a new way of seeing employer-employee relationships by introducing the concept of perceived exploitative employee-organization relationships, distinguish it from related concepts, and conduct five studies to develop a scale and test our theoretical model of the effects of such employee perceptions. Contributing to the Employee-Organization Relationships and workplace emotions literatures, perceived exploitation is defined as employees’ perceptions that they have been purposefully taken advantage of in their relationship with the organization, to the benefit of the organization itself. We propose and find that such perceptions are associated with both outward-focused emotions of anger and hostility toward the organization and inward-focused ones of shame and guilt at remaining in an exploitative job. In two studies including construction workers and a time-lagged study of medical residents, we find that the emotions of anger and hostility partially mediate the effects of perceived exploitation on employee engagement, revenge against the organization, organizational commitment, and turnover intentions, whereas the emotions of shame and guilt partially mediate the effects of perceived exploitation on employee burnout, silence, and psychological withdrawal

The Link Between Management Behavior and Ethical Philosophy in the Wake of the Enron Convictions

ethics, scandals, philosophy, Enron,

Retroviral b‐Zip protein (HBZ) contributes to the release of soluble and exosomal immune checkpoint molecules in the context of neuroinflammation

Abstract HTLV‐I‐associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a chronic, progressive, neuroinflammatory demyelinating condition of the spinal cord. We have previously shown that aberrant expression and activity of immune checkpoint (ICP) molecules such as PD‐1 and PD‐L1/PD‐L2, negatively associates with the cytolytic potential of T cells in individuals with HAM/TSP. Interestingly, ICPs can exist in a soluble cell‐free form and can be carried on extracellular vesicles (EVs) and exosomes (small EVs, <300 nm) while maintaining their immunomodulatory activity. Therefore, we investigated the role of soluble and exosomal ICPs in HTLV‐1 associated neuroinflammation. For the very first time, we demonstrate a unique elevated presence of several stimulatory (CD27, CD28, 4‐1BB) and inhibitory (BTLA, CTLA‐4, LAG‐3, PD‐1, PD‐L2) ICP receptors in HAM/TSP sera, and in purified exosomes from a HAM/TSP‐derived HTLV‐1‐producing (OSP2) cells. These ICPs were found to be co‐localized with the endosomal sorting complex required for transport (ESCRT) pathway proteins and exhibited functional binding with their respective ligands. Viral proteins and cytokines (primarily IFNγ) were found to be present in purified exosomes. IFNγ exposure enhanced the release of ICP molecules while antiretroviral drugs (Azidothymidine and Lopinavir) significantly inhibited this process. HTLV‐1 b‐Zip protein (HBZ) has been linked to factors that enhance EV release and concurrent knockdown here led to the reduced expression of ESCRT associated genes (e.g., Hrs, Vsp4, Alix, Tsg101) as well as abrogated the release of ICP molecules, suggesting HBZ involvement in this process. Moreso, exosomes from OSP2 cells adversely affected CD8 T‐cell functions by diminishing levels of cytokines and cytotoxic factors. Collectively, these findings highlight exosome‐mediated immunomodulation of T‐cell functions with HBZ and ESCRT pathways as an underlying mechanism in the context of HTLV‐1‐induced neuroinflammation

The Relation Between Policies Concerning Corporate Social Responsibility (CSR) and Philosophical Moral Theories – An Empirical Investigation

common-sense morality, CSR policies, ethical egoism, libertarianism, philosophical moral theories, utilitarianism,