Honey bees (Apis mellifera) are agriculturally important pollinators that have been recently at risk to severe colony losses. A variety of parasites and pathogens have been linked to colony decline, including the microsporidian parasite Nosema ceranae. While fumagillin has been used to control nosemosis in managed honey bee colonies for decades, research shows that this antibiotic poses a toxic threat and that its efficacy against N. ceranae is uncertain. There is certainly a demand for a new veterinary medication to treat honey bee colonies infected with N. ceranae. In this review, recent scientific advances in controlling N. ceranae infections in honey bees are summarized.

Mesenchymal stromal cells (MSCs) are widely recognized to possess potent immunomodulatory activity, as well as to stimulate repair and regeneration of diseased or damaged tissue. These fundamental properties suggest important applications in hematopoietic cell transplantation. Although the mechanisms of therapeutic activity in vivo are yet to be fully elucidated, MSCs seem to suppress lymphocytes by paracrine mechanisms, including secreted mediators and metabolic modulators. Most recently, host macrophage engulfment of apoptotic MSCs has emerged as an important contributor to the immune suppressive microenvironment. Although bone marrow–derived MSCs are the most commonly studied, the tissue source of MSCs may be a critical determinant of immunomodulatory function. The key application of MSC therapy in hematopoietic cell transplantation is to prevent or treat graft-versus-host disease (GVHD). The pathogenesis of GVHD reveals multiple potential targets. Moreover, the recently proposed concept of tissue tolerance suggests a new possible mechanism of MSC therapy for GVHD. Beyond GVHD, MSCs may facilitate hematopoietic stem cell engraftment, which could gain greater importance with increasing use of haploidentical transplantation. Despite many challenges and much doubt, commercial MSC products for pediatric steroid-refractory GVHD have been licensed in Japan, conditionally licensed in Canada and New Zealand, and have been recommended for approval by an FDA Advisory Committee in the United States. Here, we review key historical data in the context of the most salient recent findings to present the current state of MSCs as adjunct cell therapy in hematopoietic cell transplantation.

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BackgroundAnti-PD-1 immune checkpoint blockade is approved for first-line treatment of recurrent/metastatic head and neck squamous cell carcinoma (HNSCC), but few patients respond. Statin drugs (HMG-CoA reductase inhibitors) are associated with superior survival in several cancer types, including HNSCC. Emerging data suggest that manipulation of cholesterol may enhance some aspects of antitumor immunity.MethodsWe used syngeneic murine models (mouse oral cancer, MOC1 and TC-1) to investigate our hypothesis that a subset of statin drugs would enhance antitumor immunity and delay tumor growth.ResultsUsing an ex vivo coculture assay of murine cancer cells and tumor infiltrating lymphocytes, we discovered that all seven statin drugs inhibited tumor cell proliferation. Simvastatin and lovastatin also enhanced T-cell killing of tumor cells. In mice, daily oral simvastatin or lovastatin enhanced tumor control and extended survival when combined with PD-1 blockade, with rejection of MOC1 tumors in 30% of mice treated with lovastatin plus anti-PD-1. Results from flow cytometry of tumors and tumor-draining lymph nodes suggested T cell activation and shifts from M2 to M1 macrophage predominance as potential mechanisms of combination therapy.ConclusionsThese results suggest that statins deserve further study as well-tolerated, inexpensive drugs that may enhance responses to PD-1 checkpoint blockade and other immunotherapies for HNSCC.

Mesenchymal stromal cells (MSCs) are spindle-shaped, plastic-adherent cells in vitro with potent immunosuppressive activity both in vitro and in vivo. MSCs have been employed as a cellular immunotherapy in diverse preclinical models and clinical trials, but most commonly as agents for the prophylaxis or therapy of graft versus host disease after hematopoietic cell transplantation. In addition to the oft studied secreted cytokines, several metabolic pathways intrinsic to MSCs, notably indoleamine 2,3-dioxygenase, prostaglandin E2, hypoxia-inducible factor 1 α, heme oxygenase-1, as well as energy-generating metabolism, have been shown to play roles in the immunomodulatory activity of MSCs. In this review, we discuss these key metabolic pathways in MSCs which have been reported to contribute to MSC therapeutic effects in the setting of hematopoietic cell transplantation and graft versus host disease. Understanding the contribution of MSC metabolism to immunomodulatory activity may substantially inform the development of future clinical applications of MSCs.