Antibody-mediated targeting of TNFR2 activates CD8+T cells in mice and promotes antitumor immunity
(2019)
Tumor necrosis factor receptor 2 (TNFR2) is the alternate receptor for TNF and can mediate both pro- and anti-inflammatory activities of T cells. Although TNFR2 has been linked to enhanced suppressive activity of regulatory T cells (Tregs) in autoimmune diseases, the viability of TNFR2 as a target for cancer immunotherapy has been underappreciated. Here, we show that new murine monoclonal anti-TNFR2 antibodies yield robust antitumor activity and durable protective memory in multiple mouse cancer cell line models. The antibodies mediate potent Fc-dependent T cell costimulation and do not result in significant depletion of Tregs. Corresponding human agonistic monoclonal anti-TNFR2 antibodies were identified and also had antitumor effects in humanized mouse models. Anti-TNFR2 antibodies could be developed as a novel treatment option for patients with cancer.
Accounting for how the human mind represents the internal and external world is a crucial feature of many theories of human cognition. Central to this question is the distinction between modal as opposed to amodal representational formats. It has often been assumed that one but not both of these two types of representations underlie processing in specific domains of cognition (e.g., perception, mental imagery, and language). However, in this paper, we suggest that both formats play a major role in most cognitive domains. We believe that a comprehensive theory of cognition requires a solid understanding of these representational formats and their functional roles within and across different domains of cognition, the developmental trajectory of these representational formats, and their role in dysfunctional behavior. Here we sketch such an overarching perspective that brings together research from diverse subdisciplines of psychology on modal and amodal representational formats so as to unravel their functional principles and their interactions.
