β-Adrenergic signaling blocks murine CD8 + T-cell metabolic reprogramming during activation: a mechanism for immunosuppression by adrenergic stress

This study demonstrates that one mechanism by which β2-AR signaling can inhibit CD8+ T-cell activation  is by suppressing the required metabolic reprogramming events which accompany activation of these immune cells and thus reveals a new mechanism by which adrenergic stress can suppress the effector activity of immune cells.
Source: Cancer Immunology, Immunotherapy - Category: Cancer & Oncology Source Type: research

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Catecholamines released by sympathetic nerves can activate adrenergic receptors present on nearly every cell type, including myeloid-derived suppressor cells (MDSCs). Using in vitro systems, murine tumor models in wild-type and genetically modified (β2-AR–/–) mice, and adoptive transfer approaches, we found that the degree of β2-AR signaling significantly influences MDSC frequency and survival in tumors and other tissues. It also modulates their expression of immunosuppressive molecules such as arginase-I and PD-L1 and alters their ability to suppress the proliferation of T cells. The regulatory funct...
Source: Journal of Clinical Investigation - Category: Biomedical Science Authors: Source Type: research
Mounting preclinical and clinical evidence continues to support a role for the neuroendocrine system in the modulation of tumor biology and progression. Several studies have shown data supporting a link between chronic stress and cancer progression. Dysregulation of the sympathetic nervous system (SNS) and the hypothalamic-pituitary-adrenal (HPA) axis has been implicated in promoting angiogenesis, tumor cell proliferation and survival, alteration of the immune response and exacerbating inflammatory networks in the tumor microenvironment. Here, we review how SNS and HPA dysregulation contributes to disturbances in immune ce...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Our world has never witnessed a time of greater promise for improving human health. Many of today’s health advances have stemmed from a long arc of discovery that begins with strong, steady support for basic science. In large part because of fundamental research funded by the National Institutes of Health (NIH), which traces its roots to 1887, Americans are living longer, healthier lives. Life expectancy for a baby born in the U.S. has risen from 47 years in 1900 to more than 78 years today. Among the advances that have helped to make this possible are a 70% decline in the U.S. death rate from cardiovascular disease ...
Source: TIME: Science - Category: Science Authors: Tags: Uncategorized Healthcare medicine Source Type: news
ConclusionsImmune checkpoint inhibitors can have a wide range of unusual, rare irAEs, including neurotoxicity such as AAG. Clinicians should maintain suspicion for this toxicity so that treatment can be rapidly provided to avoid disability.
Source: Journal for Immunotherapy of Cancer - Category: Cancer & Oncology Source Type: research
In this study, we report the age-associated differences between fetal MSC (fMSC) populations and MSCs isolated from elderly donors with respect to their transcriptomes. We successfully reprogrammed fMSCs (55 days post conception) and adult MSC (aMSC; 60-74 years) to iPSCs and, subsequently, generated the corresponding iMSCs. In addition, iMSCs were also derived from ESCs. The iMSCs were similar although not identical to primary MSCs. We unraveled a putative rejuvenation and aging gene expression signature. We show that iMSCs irrespective of donor age and cell type re-acquired a similar secretome to that of th...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Reena Goswami1, Gayatri Subramanian2, Liliya Silayeva1, Isabelle Newkirk1, Deborah Doctor1, Karan Chawla2, Saurabh Chattopadhyay2, Dhyan Chandra3, Nageswararao Chilukuri1 and Venkaiah Betapudi1,4* 1Neuroscience Branch, Research Division, United States Army Medical Research Institute of Chemical Defense, Aberdeen, MD, United States 2Department of Medical Microbiology and Immunology, University of Toledo College of Medicine and Life Sciences, Toledo, OH, United States 3Roswell Park Comprehensive Cancer Center, Buffalo, NY, United States 4Department of Physiology and Biophysics, Case Western Reserve University, Clev...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
In this study, we investigated the impact of the human ALK-F1174L mutation in vivo on sympathetic neuroblast differentiation using Sox10-Cre;LSL-ALK-F1174L mice. The aim was to improve our understanding of the implication of ALK deregulated signaling in the initial steps of NB genesis. Results ALK-F1174L Causes Embryonic Lethality When Expressed in NCCs Prior to SA Lineage Commitment To assess the impact of the human ALK-F1174L activating mutation on the development and differentiation of the SNS, Sox10-Cre;LSL-ALK-F1174L embryos were generated. This model allowed to restrict the expression of the ALK-F1174L variant to ...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Publication date: Available online 9 November 2018Source: Biochimica et Biophysica Acta (BBA) - Reviews on CancerAuthor(s): Dan Liu, Xiaoxi Li, Xintian Chen, Yu Sun, Anqun Tang, Zhongwei Li, Junnian Zheng, Ming ShiAbstractThe treatment of cancer has made great progress. However, drug resistance remains problematic. Multiple physiologic processes of tumor development can be dominated by central and sympathetic nervous systems. The interactions between the nervous system, immune system, and tumor occur consistently and dynamically. Recent evidence suggests that nerves and neural signals are intimately involved in the develop...
Source: Biochimica et Biophysica Acta (BBA) Reviews on Cancer - Category: Cancer & Oncology Source Type: research
Fight Aging! provides a weekly digest of news and commentary for thousands of subscribers interested in the latest longevity science: progress towards the medical control of aging in order to prevent age-related frailty, suffering, and disease, as well as improvements in the present understanding of what works and what doesn't work when it comes to extending healthy life. Expect to see summaries of recent advances in medical research, news from the scientific community, advocacy and fundraising initiatives to help speed work on the repair and reversal of aging, links to online resources, and much more. This content is...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Johnson &Johnson (NYSE:JNJ) opened its latest life science incubator in New York City, the healthcare giant said today. The 30,000-square-foot JLabs @ NYC is a collaboration between Johnson &Johnson Innovation, New York State and the New York Genome Center. Sited at the genome center in SoHo, the incubator is home to 26 startups and has room for four more, New Brunswick, N.J.-based J&J said. “Johnson &Johnson has deep entrepreneurial roots in New York and we are pleased to see our unique JLabs model applied in this rich ecosystem to foster the creation of new healthcare innovations that have the pote...
Source: Mass Device - Category: Medical Devices Authors: Tags: Funding Roundup Research & Development johnsonandjohnson Source Type: news
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