Targeting nucleic acid sensors in tumor cells to reprogram biogenesis and RNA cargo of extracellular vesicles for T cell-mediated cancer immunotherapy.

Tumor-derived extracellular vesicles (EVs) have been associated with immune evasion and tumor progression. We show that the RNA-sensing receptor RIG-I within tumor cells governs biogenesis and immunomodulatory function of EVs. Cancer-intrinsic RIG-I activation releases EVs, which mediate dendritic cell maturation and T cell antitumor immunity, synergizing with immune checkpoint blockade. Intact RIG-I, autocrine interferon signaling, and the GTPase Rab27a in tumor cells are required for biogenesis of immunostimulatory EVs. Active intrinsic RIG-I signaling governs composition of the tumor EV RNA cargo including small non-coding stimulatory RNAs. High transcriptional activity of EV pathway genes and RIG-I in melanoma samples associate with prolonged patient survival and beneficial response to immunotherapy. EVs generated from human melanoma after RIG-I stimulation induce potent antigen-specific T cell responses. We thus define a molecular pathway that can be targeted in tumors to favorably alter EV immunomodulatory function. We propose "reprogramming" of tumor EVs as a personalized strategy for T cell-mediated cancer immunotherapy.

The Benefits of an Augmented Reality Magic Mirror System for Integrated Radiology Teaching in Gross Anatomy.

Early exposure to radiological cross-section images during introductory anatomy and dissection courses increases students' understanding of both anatomy and radiology. Novel technologies such as augmented reality (AR) offer unique advantages for an interactive and hands-on integration with the student at the center of the learning experience. In this article, the benefits of a previously proposed AR Magic Mirror system are compared to the Anatomage, a virtual dissection table as a system for combined anatomy and radiology teaching during a two-semester gross anatomy course with 749 first-year medical students, as well as a follow-up elective course with 72 students. During the former, students worked with both systems in dedicated tutorial sessions which accompanied the anatomy lectures and provided survey-based feedback. In the elective course, participants were assigned to three groups and underwent a self-directed learning session using either Anatomage, Magic Mirror, or traditional radiology atlases. A pre- and posttest design with multiple choice questions revealed significant improvements in test scores between the two tests for both the Magic Mirror and the group using radiology atlases, while no significant differences in test scores were recorded for the Anatomage group. Furthermore, especially students with low mental rotation test (MRT) scores benefited from the Magic Mirror and Anatomage and achieved significantly higher posttest scores compared to students with a low MRT score in the theory group. Overall, the results provide supporting evidence that the Magic Mirror system achieves comparable results in terms of learning outcome to established anatomy learning tools such as Anatomage and radiology atlases.