The dysregulated expression of immune checkpoint molecules enables cancer cells to evade immune destruction. While blockade of inhibitory immune checkpoints like PD-L1 forms the basis of current ca...Show moreThe dysregulated expression of immune checkpoint molecules enables cancer cells to evade immune destruction. While blockade of inhibitory immune checkpoints like PD-L1 forms the basis of current cancer immunotherapies, a deficiency in costimulatory signals can render these therapies futile. CD58, a costimulatory ligand, plays a crucial role in antitumor immune responses, but the mechanisms controlling its expression remain unclear. Using two systematic approaches, we reveal that CMTM6 positively regulates CD58 expression. Notably, CMTM6 interacts with both CD58 and PD-L1, maintaining the expression of these two immune checkpoint ligands with opposing functions. Functionally, the presence of CMTM6 and CD58 on tumor cells significantly affects T cell-tumor interactions and response to PD-L1−PD-1 blockade. Collectively, these findings provide fundamental insights into CD58 regulation, uncover a shared regulator of stimulatory and inhibitory immune checkpoints, and highlight the importance of tumor-intrinsic CMTM6 and CD58 expression in antitumor immune responses. Show less
Smart wearables are increasingly used to help people deal with stress. Still, a less explored area of research in this field concerns the partnerships that smart wearables can take on when engaging... Show moreSmart wearables are increasingly used to help people deal with stress. Still, a less explored area of research in this field concerns the partnerships that smart wearables can take on when engaging people in stress-coping activities. To facilitate further understanding of the human-wearable partnerships, we designed Grippy, a smart wearable system composed of a physical glove and a smartphone application to help the wearer actively explore and cope with stress in daily situations. We introduced Grippy, as a speculative probe, to six participants (four master students and two university employees) who wore it for five successive days. Participants were interviewed about their use experience of Grippy during and after these five days. Qualitative data collected from the interviews was interpreted regarding how Grippy could fit into people’s stress-coping activities across different daily contexts and what kinds of partnerships with the smart wearable were perceived by the participants. In addition, we reflect on the design issues that led to the mismatch between our design intentions and people’s actual use experiences. We discuss how these results have deepened our understanding of human-wearable partnerships in the context of stress management and the usability issues that might hinder the expression and acceptance of smart wearables designed as partners. We end the discussion by reflecting on the implications of smart wearables as partners in mental healthcare. Show less
