Glutamine is critical for the maintenance of type 1 conventional dendritic cells in normal tissue and the tumor microenvironment.

Proliferating tumor cells take up glutamine for anabolic processes, engendering glutamine deficiency in the tumor microenvironment. How this might impact immune cells is not well understood. Using multiple mouse models of soft tissue sarcomas, glutamine antagonists, as well as genetic and pharmacological inhibition of glutamine utilization, we found that the number and frequency of conventional dendritic cells (cDCs) is dependent on microenvironmental glutamine levels.

Glutamine availability regulates cDC subsets in tissue.

Unlabelled: Proliferating tumor cells take up glutamine for anabolic processes engendering glutamine deficiency in the tumor microenvironment. How this might impact immune cells is not well understood. Using multiple mouse models of soft tissue sarcomas, glutamine antagonists, as well as genetic and pharmacological inhibition of glutamine utilization, we found that the number and frequency of conventional dendritic cells (cDC) is dependent on microenvironmental glutamine levels.

RALDH1 Inhibition Shows Immunotherapeutic Efficacy in Hepatocellular Carcinoma.

Globally, hepatocellular carcinoma (HCC) is one of the most commonly diagnosed cancers and a leading cause of cancer-related death. We previously identified an immune evasion pathway whereby tumor cells produce retinoic acid (RA) to promote differentiation of intratumoral monocytes into protumor macrophages. Retinaldehyde dehydrogenase 1 (RALDH1), RALDH2, and RALDH3 are the three isozymes that catalyze RA biosynthesis.

Tumor microenvironmental nutrients, cellular responses, and cancer.

Over the last two decades, the rapidly expanding field of tumor metabolism has enhanced our knowledge of the impact of nutrient availability on metabolic reprogramming in cancer. Apart from established roles in cancer cells themselves, various nutrients, metabolic enzymes, and stress responses are key to the activities of tumor microenvironmental immune, fibroblastic, endothelial, and other cell types that support malignant transformation. In this article, we review our current understanding of how nutrient availability affects metabolic pathways and responses in both cancer and "stromal" cells, by dissecting major examples and their regulation of cellular activity.

ASS1 and ASL suppress growth in clear cell renal cell carcinoma via altered nitrogen metabolism.

Background: Kidney cancer is a common adult malignancy in the USA. Clear cell renal cell carcinoma (ccRCC), the predominant subtype of kidney cancer, is characterized by widespread metabolic changes. Urea metabolism is one such altered pathway in ccRCC.

Tumor-Derived Retinoic Acid Regulates Intratumoral Monocyte Differentiation to Promote Immune Suppression.

The immunosuppressive tumor microenvironment (TME) is a major barrier to immunotherapy. Within solid tumors, why monocytes preferentially differentiate into immunosuppressive tumor-associated macrophages (TAMs) rather than immunostimulatory dendritic cells (DCs) remains unclear. Using multiple murine sarcoma models, we find that the TME induces tumor cells to produce retinoic acid (RA), which polarizes intratumoral monocyte differentiation toward TAMs and away from DCs via suppression of DC-promoting transcription factor Irf4.

Programmed Death Ligand 1 Is a Negative Prognostic Marker in Recurrent Isocitrate Dehydrogenase-Wildtype Glioblastoma.

Background: Checkpoint inhibition has demonstrated clinical efficacy in a variety of solid tumors. Reports of programmed death ligand 1 (PD-L1) expression in glioblastoma are highly variable (ranging from 6% to 88%) and its role as a prognostic marker has yielded conflicting results.

Objective: To validate the prevalence and prognostic role of PD-L1 expression in a large cohort of diffuse gliomas according to the 2016 revised WHO classification.

Patient Blood Management in the Intensive Care Unit.

Patient Blood Management underscores a fundamental shift from a product-centered approach to a patient-centric approach through timely application of evidence-based medical and surgical concepts designed to maintain hemoglobin concentration, optimize hemostasis, and minimize blood loss in an effort to improve patient outcome. In this concept, allogeneic blood transfusion is not viewed as the treatment of default for anemic patients, but one among many treatment modalities that should be weighed based on its merits-potentials risks and benefits-for the individual patient in the context of other alternatives. Patient blood management provides a multidisciplinary framework for patient-centered decision making with strategies focusing on the management of anemia, optimization of coagulation and hemostasis, and utilization of blood conservation modalities.

Anesthesia for Patients with Anemia.

Anemia is a common and often ignored condition in surgical patients. Anemia is usually multifactorial and iron deficiency and inflammation are commonly involved. An exacerbating factor in surgical patients is iatrogenic blood loss.

Transfusion practices and infectious risks.

Transfusion-transmitted infections remain among the most-feared complications of allogeneic blood transfusion. Thanks to several strategies including donor screening and deferral, blood testing and pathogen inactivation, their risks have reached all-time low levels, particularly in developed nations. Nonetheless, new and emerging infections remain a threat that is likely to exacerbate in the coming years with continued globalization and climate change.

Risks of Anemia in Cardiac Surgery Patients.

Anemia is an common condition in patients undergoing cardiac surgery, and it is often present in one quarter to half of patients at admission. Several studies have indicated that anemia is a major risk factor for worse outcomes, including increased risk of mortality and major morbidity and prolonged hospitalization. Anemia is a leading reason for use of allogeneic blood transfusions.

From bloodless surgery to patient blood management.

Safety and efficacy concerns of allogeneic blood transfusions and their impact on patient outcomes and associated staggering costs and restricted supply have fueled the quest for other modalities and strategies to reduce use of blood components. Patient blood management focuses on multidisciplinary and multimodal preventive measures to reduce or obviate the need for transfusions and ultimately to improve the clinical outcomes of patients. Patient blood management strategies can be applied at every stage of care to surgical and nonsurgical patients, and they generally fall under one of these three categories (the so-called pillars of blood management): optimizing hematopoiesis and appropriate management of anemia, minimizing bleeding and blood loss, and harnessing and optimizing physiological tolerance of anemia through employing all available modalities while treatment is initiated.

Intramuscular rocuronium in infants and children: a multicenter study to evaluate tracheal intubating conditions, onset, and duration of action.

Background: This multicenter, assessor-blinded, randomized study was done to confirm and extend a pilot study showing that intramuscular rocuronium can provide adequate tracheal intubating conditions in infants (2.5 min) and children (3 min) during halothane anesthesia.

Methods: Thirty-eight infants (age range, 3-12 months) and 38 children (age range, 1 to 5 yr) classified as American Society of Anesthesiologists physical status 1 and 2 were evaluated at four investigational sites.