Citations

Abstract Pancreatic ductal adenocarcinoma (PDAC) is unresponsive to immune checkpoint therapies largely due to immunosuppression mediated by myeloid and lymphoid cells. Effective treatment strategies require, in addition to immune stimulation, the depletion of these immunosuppressive cells and their interactions. Here, we demonstrate for the first time, that a single verteporfin-based photodynamic therapy (PDT) treatment triples median survival in a KPC-PDAC model when combined with anti-PD1 therapy. Mechanistically, apart from reducing CK19 + tumor cells, PDT depletes immunosuppressive myeloid (CD11c+) and lymphoid (FOXP3+) cell populations, by ~ 4- and ~ 18.4-folds, respectively. PDT further disrupts interactions between these immunosuppressive cells, attenuating a key immune-tolerance axis. At the systemic level, PDT reduces splenic immunosuppression through modulation of tumor-derived cytokines. Within this reprogrammed immune-landscape, anti–PD-1 therapy elicits robust CD8 + T-cell responses, reflected by an ~ 6.7-fold increase in the intratumoral CD8+/Treg ratio. Collectively, these findings establish verteporfin-PDT as an immune-priming strategy that complements anti–PD-1 therapy by alleviating immunosuppression in PDAC.

Dynamic fluid and solute transportation across the arachnoid barrier in the meninges of healthy participants was measured by tracking intravenous gadolinium-based contrast agent entering cerebrospinal fluid from dural blood vessels using dynamic dual-spin-echo perfusion MRI.

Kidney dysfunction after heart transplantation (HT) is associated with significant morbidity and mortality. Recipient and perioperative factors may all influence the risk of kidney injury. Furthermore, data suggest that the incidence of kidney dysfunction, both acute and chronic, is increasing after the implementation of the United States’ 2018 allocation system due to increasing use of temporary mechanical circulatory support and changing recipient characteristics. While data are robust regarding nephroprotective therapies such as renin-angiotensin-aldosterone system inhibition and SGLT2i (sodium-glucose cotransporter 2 inhibitors) to minimize the progression of chronic kidney disease in patients with heart failure, data in HT recipients are beginning to emerge. This state-of-the-art review will critically examine the existing literature regarding the epidemiology of kidney dysfunction after HT, mitigation strategies for acute kidney injury and chronic kidney disease, including pharmacotherapeutics, the need for kidney transplantation after HT, and practical next steps for the larger HT community.