Abstract:
:Cellular immunity has an inherent high level of functional heterogeneity. Capturing the full spectrum of these functions requires analysis of large numbers of effector molecules from single cells. We report a microfluidic platform designed for highly multiplexed (more than ten proteins), reliable, sample-efficient (∼1 × 10(4) cells) and quantitative measurements of secreted proteins from single cells. We validated the platform by assessment of multiple inflammatory cytokines from lipopolysaccharide (LPS)-stimulated human macrophages and comparison to standard immunotechnologies. We applied the platform toward the ex vivo quantification of T cell polyfunctional diversity via the simultaneous measurement of a dozen effector molecules secreted from tumor antigen-specific cytotoxic T lymphocytes (CTLs) that were actively responding to tumor and compared against a cohort of healthy donor controls. We observed profound, yet focused, functional heterogeneity in active tumor antigen-specific CTLs, with the major functional phenotypes quantitatively identified. The platform represents a new and informative tool for immune monitoring and clinical assessment.
journal_name
Nat Medjournal_title
Nature medicineauthors
Ma C,Fan R,Ahmad H,Shi Q,Comin-Anduix B,Chodon T,Koya RC,Liu CC,Kwong GA,Radu CG,Ribas A,Heath JRdoi
10.1038/nm.2375subject
Has Abstractpub_date
2011-06-01 00:00:00pages
738-43issue
6eissn
1078-8956issn
1546-170Xpii
nm.2375journal_volume
17pub_type
杂志文章相关文献
NATURE MEDICINE文献大全abstract::Photoreceptor ciliopathies constitute the most common molecular mechanism of the childhood blindness Leber congenital amaurosis. Ten patients with Leber congenital amaurosis carrying the c.2991+1655A>G allele in the ciliopathy gene centrosomal protein 290 (CEP290) were treated (ClinicalTrials.gov no. NCT03140969 ) wit...
journal_title:Nature medicine
pub_type: 临床试验,杂志文章
doi:10.1038/s41591-018-0295-0
更新日期:2019-02-01 00:00:00
abstract::Familial hypertrophic cardiomyopathy (FHC) is a genetic disorder resulting from mutations in genes encoding sarcomeric proteins. This typically induces hyperdynamic ejection, impaired relaxation, delayed early filling, myocyte disarray and fibrosis, and increased chamber end-systolic stiffness. To better understand th...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/6549
更新日期:1999-03-01 00:00:00
abstract::Retinal ischemia can cause vision-threatening pathological neovascularization. The mechanisms of retinal ischemia are not fully understood, however. Here we have shown that leukocytes prune the retinal vasculature during normal development and obliterate it in disease. Beginning at postnatal day 5 (P5) in the normal r...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm877
更新日期:2003-06-01 00:00:00
abstract::How high salt intake increases blood pressure is a key question in the study of hypertension. Salt intake induces increased renal sympathetic activity resulting in sodium retention. However, the mechanisms underlying the sympathetic control of renal sodium excretion remain unclear. In this study, we found that β(2)-ad...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm.2337
更新日期:2011-05-01 00:00:00
abstract::Metabolic reprograming is an emerging hallmark of tumor biology and an actively pursued opportunity in discovery of oncology drugs. Extensive efforts have focused on therapeutic targeting of glycolysis, whereas drugging mitochondrial oxidative phosphorylation (OXPHOS) has remained largely unexplored, partly owing to a...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/s41591-018-0052-4
更新日期:2018-07-01 00:00:00
abstract::Deep brain stimulation (DBS) is a widely used neurosurgical approach to treating tremor and other movement disorders. In addition, the use of DBS in a number of psychiatric diseases, including obsessive-compulsive disorders and depression, is currently being tested. Despite the rapid increase in the number of individu...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm1693
更新日期:2008-01-01 00:00:00
abstract::The tumor suppressor p53 inhibits tumor growth primarily through its ability to induce apoptosis. Mutations in p53 occur in at least 50% of human tumors. We hypothesized that reactivation of mutant p53 in such tumors should trigger massive apoptosis and eliminate the tumor cells. To test this, we screened a library of...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm0302-282
更新日期:2002-03-01 00:00:00
abstract::Spinal sensorimotor networks that are functionally disconnected from the brain because of spinal cord injury (SCI) can be facilitated via epidural electrical stimulation (EES) to restore robust, coordinated motor activity in humans with paralysis1-3. Previously, we reported a clinical case of complete sensorimotor par...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/s41591-018-0175-7
更新日期:2018-11-01 00:00:00
abstract::Recurrent medulloblastoma and ependymoma are universally lethal, with no approved targeted therapies and few candidates presently under clinical evaluation. Nearly all recurrent medulloblastomas and posterior fossa group A (PFA) ependymomas are located adjacent to and bathed by the cerebrospinal fluid, presenting an o...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/s41591-020-0827-2
更新日期:2020-05-01 00:00:00
abstract::Reactive oxygen species (ROS) induce chemokines responsible for the recruitment of inflammatory cells to sites of injury or infection. Here we show that the plasma membrane Ca(2+)-permeable channel TRPM2 controls ROS-induced chemokine production in monocytes. In human U937 monocytes, hydrogen peroxide (H(2)O(2)) evoke...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm1758
更新日期:2008-07-01 00:00:00
abstract::The role of nitric oxide (NO) in the genesis of cerebral malaria is controversial. Most investigators propose that the unfortunate consequence of the high concentrations of NO produced to kill the parasite is the development of cerebral malaria. Here we have tested this high NO bioavailability hypothesis in the settin...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm1499
更新日期:2006-12-01 00:00:00
abstract::Colon cancer is a clinically diverse disease. This heterogeneity makes it difficult to determine which patients will benefit most from adjuvant therapy and impedes the development of new targeted agents. More insight into the biological diversity of colon cancers, especially in relation to clinical features, is theref...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm.3174
更新日期:2013-05-01 00:00:00
abstract::Evolutionary patterns of virus replication and distribution in lymphoid tissue during the early phases of HIV infection have not been delineated. Lymph node (LN) biopsies were excised from patients at different times after the estimated time of primary infection. Within 3 months of the acute viral syndrome, HIV was mo...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm0398-341
更新日期:1998-03-01 00:00:00
abstract::By convention, CD4+ T lymphocytes recognize foreign and self peptides derived from internalized antigens in combination with major histocompatibility complex class II molecules. Alternative pathways of epitope production have been identified, but their contributions to host defense have not been established. We show h...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm.3958
更新日期:2015-10-01 00:00:00
abstract::Disruption of systemic homeostasis by either chronic or acute stressors, such as obesity1 or surgery2, alters cancer pathogenesis. Patients with cancer, particularly those with breast cancer, can be at increased risk of cardiovascular disease due to treatment toxicity and changes in lifestyle behaviors3-5. While eleva...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/s41591-020-0964-7
更新日期:2020-09-01 00:00:00
abstract::We and others have postulated that a constant number of T lymphocytes is normally maintained without regard to CD4+ or CD8+ phenotype ('blind' T-cell homeostasis). Here we confirm essentially constant T-cell levels (despite marked decline in CD4+ T cells and increase in CD8+ T cells) in homosexual men with incident hu...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm0795-674
更新日期:1995-07-01 00:00:00
abstract::We have designed short peptides composed of two functional domains, one a tumor blood vessel 'homing' motif and the other a programmed cell death-inducing sequence, and synthesized them by simple peptide chemistry. The 'homing' domain was designed to guide the peptide to targeted cells and allow its internalization. T...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/12469
更新日期:1999-09-01 00:00:00
abstract::Mesenchymal stem cells can give rise to several cell types, but varying results depending on isolation methods and tissue source have led to controversies about their usefulness in clinical medicine. Here we show that vascular endothelial cells can transform into multipotent stem-like cells by an activin-like kinase-2...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm.2252
更新日期:2010-12-01 00:00:00
abstract::The human protein apolipoprotein B mRNA-editing enzyme-catalytic polypeptide-like-3G (APOBEC3G), also known as CEM-15, mediates a newly described form of innate resistance to retroviral infection by catalyzing the deamination of deoxycytidine to deoxyuridine in viral cDNA replication intermediates. Because DNA deamina...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm945
更新日期:2003-11-01 00:00:00
abstract::Cold exposure may be a potential therapy for diabetes by increasing brown adipose tissue (BAT) mass and activity. Here we report that 10 d of cold acclimation (14-15 °C) increased peripheral insulin sensitivity by ∼43% in eight type 2 diabetes subjects. Basal skeletal muscle GLUT4 translocation markedly increased, wit...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm.3891
更新日期:2015-08-01 00:00:00
abstract::Recent studies of subjects infected with human immunodeficiency virus (HIV-1) have produced conflicting results about the extent of reconstitution possible in the CD4+ lymphocyte repertoire after highly active antiretroviral therapy (HAART). The effect of HAART on the incidence of opportunistic infections will probabl...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm0898-953
更新日期:1998-08-01 00:00:00
abstract::To explore the mechanism by which herpes simplex virus (HSV)-2 infection is related to HIV-1 acquisition, we conducted in situ analysis of the cellular infiltrate from sequential biopsies of HSV-2 lesions from patients on and off antiviral therapy. CD4(+) and CD8(+) T cells and a mixed population of plasmacytoid and m...
journal_title:Nature medicine
pub_type: 临床试验,杂志文章
doi:10.1038/nm.2006
更新日期:2009-08-01 00:00:00
abstract::Migration inhibitory factor (MIF) is known to exert significant pro-inflammatory effects and has the potential to override the anti-inflammatory action of glucocorticoids. In this study we have identified significant quantities of MIF in the alveolar airspaces of patients with acute respiratory distress syndrome (ARDS...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm0397-320
更新日期:1997-03-01 00:00:00
abstract::We have previously shown that a single portal vein infusion of a recombinant adeno-associated viral vector (rAAV) expressing canine Factor IX (F.IX) resulted in long-term expression of therapeutic levels of F.IX in dogs with severe hemophilia B. We carried out a phase 1/2 dose-escalation clinical study to extend this ...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm1358
更新日期:2006-03-01 00:00:00
abstract::Autoimmune T-helper cells drive pathogenic autoantibody production in systemic lupus erythematosus (SLE), but the mechanisms maintaining those T cells are unknown. Autoreactive T cells are normally eliminated by functional inactivation (anergy) and activation-induced cell death (AICD) or apoptosis through death recept...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm1005
更新日期:2004-04-01 00:00:00
abstract::T-cell acute lymphoblastic leukemia (T-ALL), unlike other ALL types, is only infrequently associated with chromosomal aberrations, but it was recently shown that most individuals with T-ALL carry activating mutations in the NOTCH1 gene. However, the signaling pathways and target genes responsible for Notch1-induced ne...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm1524
更新日期:2007-01-01 00:00:00
abstract::Neutrophil extracellular traps (NETs) are released as neutrophils die in vitro in a process requiring hours, leaving a temporal gap that invasive microbes may exploit. Neutrophils capable of migration and phagocytosis while undergoing NETosis have not been documented. During Gram-positive skin infections, we directly ...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm.2847
更新日期:2012-09-01 00:00:00
abstract::Traditional screening for COVID-19 typically includes survey questions about symptoms and travel history, as well as temperature measurements. Here, we explore whether personal sensor data collected over time may help identify subtle changes indicating an infection, such as in patients with COVID-19. We have developed...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/s41591-020-1123-x
更新日期:2021-01-01 00:00:00
abstract::1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) produces clinical, biochemical and neuropathologic changes reminiscent of those which occur in idiopathic Parkinson's disease. 7-Nitroindazole (7-NI) is a relatively selective inhibitor of the neuronal isoform of nitric oxide synthase (NOS) that blocks MPTP neurotoxi...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm0996-1017
更新日期:1996-09-01 00:00:00
abstract::Despite the central role of the liver in the regulation of glucose and lipid metabolism, there are currently no methods to directly assess hepatic oxidative metabolism in humans in vivo. By using a new (13)C-labeling strategy in combination with (13)C magnetic resonance spectroscopy, we show that rates of mitochondria...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm.3415
更新日期:2014-01-01 00:00:00