A clinical microchip for evaluation of single immune cells reveals high functional heterogeneity in phenotypically similar T cells.

PubWeight™: 2.54‹?› | Rank: Top 2%

🔗 View Article (PMC 3681612)

Published in Nat Med on May 22, 2011

Authors

Chao Ma1, Rong Fan, Habib Ahmad, Qihui Shi, Begonya Comin-Anduix, Thinle Chodon, Richard C Koya, Chao-Chao Liu, Gabriel A Kwong, Caius G Radu, Antoni Ribas, James R Heath

Author Affiliations

1: NanoSystems Biology Cancer Center, California Institute of Technology, Pasadena, California, USA.

Associated clinical trials:

Study of Gene Modified Immune Cells in Patients With Advanced Melanoma (F5) | NCT00910650

Articles citing this

Cytometry by time-of-flight shows combinatorial cytokine expression and virus-specific cell niches within a continuum of CD8+ T cell phenotypes. Immunity (2012) 5.26

Polyfunctional responses by human T cells result from sequential release of cytokines. Proc Natl Acad Sci U S A (2011) 2.00

Single-cell technologies for monitoring immune systems. Nat Immunol (2014) 1.78

Single-cell proteomic chip for profiling intracellular signaling pathways in single tumor cells. Proc Natl Acad Sci U S A (2011) 1.76

Multifunctional T-cell analyses to study response and progression in adoptive cell transfer immunotherapy. Cancer Discov (2013) 1.68

Micro total analysis systems for cell biology and biochemical assays. Anal Chem (2011) 1.58

Conversion of danger signals into cytokine signals by hematopoietic stem and progenitor cells for regulation of stress-induced hematopoiesis. Cell Stem Cell (2014) 1.55

Systems biology and p4 medicine: past, present, and future. Rambam Maimonides Med J (2013) 1.28

JAK-STAT pathway activation in malignant and nonmalignant cells contributes to MPN pathogenesis and therapeutic response. Cancer Discov (2015) 1.26

Single-cell analysis tools for drug discovery and development. Nat Rev Drug Discov (2015) 1.23

Systems approaches to biology and disease enable translational systems medicine. Genomics Proteomics Bioinformatics (2012) 1.19

High-throughput secretomic analysis of single cells to assess functional cellular heterogeneity. Anal Chem (2013) 1.16

Evaluating cellular polyfunctionality with a novel polyfunctionality index. PLoS One (2012) 1.11

Pathogen-specific local immune fingerprints diagnose bacterial infection in peritoneal dialysis patients. J Am Soc Nephrol (2013) 1.09

Simultaneous detection of cell-secreted TNF-α and IFN-γ using micropatterned aptamer-modified electrodes. Biomaterials (2012) 1.07

Hypoxia induces a phase transition within a kinase signaling network in cancer cells. Proc Natl Acad Sci U S A (2013) 1.06

An integrated microfluidic platform for in situ cellular cytokine secretion immunophenotyping. Lab Chip (2012) 1.06

Single-cell protein analysis. Curr Opin Biotechnol (2011) 1.05

Remotely activated protein-producing nanoparticles. Nano Lett (2012) 1.01

Adoptive transfer of MART-1 T-cell receptor transgenic lymphocytes and dendritic cell vaccination in patients with metastatic melanoma. Clin Cancer Res (2014) 1.01

Highly multiplexed profiling of single-cell effector functions reveals deep functional heterogeneity in response to pathogenic ligands. Proc Natl Acad Sci U S A (2015) 0.99

Biosensors for immune cell analysis-A perspective. Biomicrofluidics (2012) 0.99

Heterogeneity in immune responses: from populations to single cells. Trends Immunol (2014) 0.98

Expression profiling of TCR-engineered T cells demonstrates overexpression of multiple inhibitory receptors in persisting lymphocytes. Blood (2013) 0.94

Primary, Adaptive, and Acquired Resistance to Cancer Immunotherapy. Cell (2017) 0.94

Reconfigurable microfluidics combined with antibody microarrays for enhanced detection of T-cell secreted cytokines. Biomicrofluidics (2013) 0.93

Micro total analysis systems: fundamental advances and applications in the laboratory, clinic, and field. Anal Chem (2012) 0.92

Multicolor multicycle molecular profiling with quantum dots for single-cell analysis. Nat Protoc (2013) 0.91

Nanowell-based immunoassays for measuring single-cell secretion: characterization of transport and surface binding. Anal Chem (2014) 0.91

Rapid multitarget immunomagnetic separation through programmable DNA linker displacement. J Am Chem Soc (2011) 0.89

An integrated microfluidic chip system for single-cell secretion profiling of rare circulating tumor cells. Sci Rep (2014) 0.88

Microchip platforms for multiplex single-cell functional proteomics with applications to immunology and cancer research. Genome Med (2013) 0.88

Systems-level analysis of innate immunity. Annu Rev Immunol (2014) 0.88

Deconstructing stem cell population heterogeneity: single-cell analysis and modeling approaches. Biotechnol Adv (2013) 0.88

Microfluidics: reframing biological enquiry. Nat Rev Mol Cell Biol (2015) 0.87

Chip in a lab: Microfluidics for next generation life science research. Biomicrofluidics (2013) 0.87

Quantitative imaging of protein secretions from single cells in real time. Biophys J (2013) 0.87

Real-time single-cell imaging of protein secretion. Sci Rep (2014) 0.87

The numerology of T cell functional diversity. Immunity (2012) 0.87

Emerging microfluidic tools for functional cellular immunophenotyping: a new potential paradigm for immune status characterization. Front Oncol (2013) 0.87

Stationary nanoliter droplet array with a substrate of choice for single adherent/nonadherent cell incubation and analysis. Proc Natl Acad Sci U S A (2014) 0.86

Multiplex serum cytokine immunoassay using nanoplasmonic biosensor microarrays. ACS Nano (2015) 0.85

Single cell functional proteomics for assessing immune response in cancer therapy: technology, methods, and applications. Front Oncol (2013) 0.84

Optofluidic detection for cellular phenotyping. Lab Chip (2012) 0.84

Nanotechnology: emerging tools for biology and medicine. Genes Dev (2013) 0.84

In silico experimentation of glioma microenvironment development and anti-tumor therapy. PLoS Comput Biol (2012) 0.84

Quantifying biomass changes of single CD8+ T cells during antigen specific cytotoxicity. PLoS One (2013) 0.84

Single-cell protein secretomic signatures as potential correlates to tumor cell lineage evolution and cell-cell interaction. Front Oncol (2013) 0.83

Preprogrammed capillarity to passively control system-level sequential and parallel microfluidic flows. Lab Chip (2013) 0.83

Self-folding single cell grippers. Nano Lett (2014) 0.82

Reconfigurable microfluidics with integrated aptasensors for monitoring intercellular communication. Lab Chip (2014) 0.81

Human NK cells licensed by killer Ig receptor genes have an altered cytokine program that modifies CD4+ T cell function. J Immunol (2014) 0.81

Recent progress using systems biology approaches to better understand molecular mechanisms of immunity. Semin Immunol (2012) 0.80

A robotics platform for automated batch fabrication of high density, microfluidics-based DNA microarrays, with applications to single cell, multiplex assays of secreted proteins. Rev Sci Instrum (2011) 0.80

Digital microfluidic immunocytochemistry in single cells. Nat Commun (2015) 0.80

Hydrogel microparticles for biosensing. Eur Polym J (2015) 0.80

High-throughput protease activity cytometry reveals dose-dependent heterogeneity in PMA-mediated ADAM17 activation. Integr Biol (Camb) (2015) 0.78

Cancer therapy: Tumours switch to resist. Nature (2012) 0.78

Travels in time: assessing the functional complexity of T cells. Proc Natl Acad Sci U S A (2012) 0.78

A microchip platform for interrogating tumor-macrophage paracrine signaling at the single-cell level. Lab Chip (2014) 0.78

Critical Points in Tumorigenesis: A Carcinogen-Initiated Phase Transition Analyzed via Single-Cell Proteomics. Small (2016) 0.77

Direct Write Protein Patterns for Multiplexed Cytokine Detection from Live Cells Using Electron Beam Lithography. ACS Nano (2015) 0.77

Hand-held and integrated single-cell pipettes. J Am Chem Soc (2014) 0.77

Label-free cytokine micro- and nano-biosensing towards personalized medicine of systemic inflammatory disorders. Adv Drug Deliv Rev (2015) 0.77

Characterizing the Switching Thresholds of Magnetophoretic Transistors. Adv Mater (2015) 0.77

A Tunable Diffusion-Consumption Mechanism of Cytokine Propagation Enables Plasticity in Cell-to-Cell Communication in the Immune System. Immunity (2017) 0.76

Microfluidics: A new tool for modeling cancer-immune interactions. Trends Cancer (2016) 0.76

Current tools for predicting cancer-specific T cell immunity. Oncoimmunology (2016) 0.76

Stochastic particle barcoding for single-cell tracking and multiparametric analysis. Small (2014) 0.76

Development of Microfluidic Systems Enabling High-Throughput Single-Cell Protein Characterization. Sensors (Basel) (2016) 0.76

Single cell proteomics in biomedicine: High-dimensional data acquisition, visualization, and analysis. Proteomics (2017) 0.76

Microarray analysis for a comprehensive immunological-status evaluation during cancer vaccine immune monitoring. J Biomed Biotechnol (2011) 0.75

Stand-Sit Microchip for High-Throughput, Multiplexed Analysis of Single Cancer Cells. Sci Rep (2016) 0.75

Microdevices for examining immunological responses of single cells to HIV. Biosci Rep (2014) 0.75

Single-neuron identification of chemical constituents, physiological changes, and metabolism using mass spectrometry. Proc Natl Acad Sci U S A (2017) 0.75

Recent Progress of Microfluidics in Translational Applications. Adv Healthc Mater (2016) 0.75

Micropatterned photodegradable hydrogels for the sorting of microbeads and cells. Angew Chem Int Ed Engl (2013) 0.75

Deconvolving heterogeneity in the CD8+ T-cell response to HIV. Curr Opin HIV AIDS (2012) 0.75

A microfluidic chip for the versatile chemical analysis of single cells. J Vis Exp (2013) 0.75

Scaling by shrinking: empowering single-cell 'omics' with microfluidic devices. Nat Rev Genet (2017) 0.75

Domain-swapped T cell receptors improve the safety of TCR gene therapy. Elife (2016) 0.75

A Label-free Technique for the Spatio-temporal Imaging of Single Cell Secretions. J Vis Exp (2015) 0.75

Single-cell profiling of dynamic cytokine secretion and the phenotype of immune cells. PLoS One (2017) 0.75

Quantitative profiling of innate immune activation by viral infection in single cells. Integr Biol (Camb) (2017) 0.75

Articles cited by this

Cluster analysis and display of genome-wide expression patterns. Proc Natl Acad Sci U S A (1998) 192.97

Inflammation and cancer. Nature (2002) 53.78

Cancer-related inflammation. Nature (2008) 34.21

Monocyte and macrophage heterogeneity. Nat Rev Immunol (2005) 24.36

Cancer regression in patients after transfer of genetically engineered lymphocytes. Science (2006) 16.96

Toll-like receptors in the induction of the innate immune response. Nature (2000) 12.23

Multifunctional TH1 cells define a correlate of vaccine-mediated protection against Leishmania major. Nat Med (2007) 11.80

Origin and physiological roles of inflammation. Nature (2008) 11.68

T-cell quality in memory and protection: implications for vaccine design. Nat Rev Immunol (2008) 11.65

Microfluidic large-scale integration. Science (2002) 7.64

Heterogeneity and cell-fate decisions in effector and memory CD8+ T cell differentiation during viral infection. Immunity (2007) 6.48

Characterization of circulating T cells specific for tumor-associated antigens in melanoma patients. Nat Med (1999) 6.09

Correlates of immune protection in HIV-1 infection: what we know, what we don't know, what we should know. Nat Med (2004) 5.49

Immunization with vaccinia virus induces polyfunctional and phenotypically distinctive CD8(+) T cell responses. J Exp Med (2007) 5.22

Phenotype and function of human T lymphocyte subsets: consensus and issues. Cytometry A (2008) 4.71

Integrated barcode chips for rapid, multiplexed analysis of proteins in microliter quantities of blood. Nat Biotechnol (2008) 4.40

Single-cell profiling identifies aberrant STAT5 activation in myeloid malignancies with specific clinical and biologic correlates. Cancer Cell (2008) 4.06

Vaccination in humans generates broad T cell cytokine responses. J Immunol (2004) 3.27

A live-cell assay to detect antigen-specific CD4+ T cells with diverse cytokine profiles. Nat Med (2005) 2.83

Functional properties and lineage relationship of CD8+ T cell subsets identified by expression of IL-7 receptor alpha and CD62L. J Immunol (2005) 2.80

DNA-encoded antibody libraries: a unified platform for multiplexed cell sorting and detection of genes and proteins. J Am Chem Soc (2007) 2.42

Human CD8(+) T-cell differentiation in response to viruses. Nat Rev Immunol (2003) 2.23

Toll-like receptor-4 (TLR4) signaling augments chemokine-induced neutrophil migration by modulating cell surface expression of chemokine receptors. Nat Med (2003) 2.14

Polyfunctional analysis of human t cell responses: importance in vaccine immunogenicity and natural infection. Springer Semin Immunopathol (2006) 2.09

Systems biology of innate immunity. Immunol Rev (2009) 1.87

Dendritic cell vaccination combined with CTLA4 blockade in patients with metastatic melanoma. Clin Cancer Res (2009) 1.81

Detailed analysis of immunologic effects of the cytotoxic T lymphocyte-associated antigen 4-blocking monoclonal antibody tremelimumab in peripheral blood of patients with melanoma. J Transl Med (2008) 1.56

Inflammation and cancer: a double-edged sword. Cancer Cell (2007) 1.52

Definition of an immunologic response using the major histocompatibility complex tetramer and enzyme-linked immunospot assays. Clin Cancer Res (2006) 1.37

Modular nucleic acid assembled p/MHC microarrays for multiplexed sorting of antigen-specific T cells. J Am Chem Soc (2009) 1.34

Characterization of subsets of CD4+ memory T cells reveals early branched pathways of T cell differentiation in humans. Proc Natl Acad Sci U S A (2005) 1.30

Protein signaling networks from single cell fluctuations and information theory profiling. Biophys J (2011) 1.21

Simultaneous infiltration of polyfunctional effector and suppressor T cells into renal cell carcinomas. Cancer Res (2009) 1.19

Heterogeneity of TLR-induced responses in dendritic cells: from innate to adaptive immunity. Immunobiology (2004) 1.18

A self-powered, one-step chip for rapid, quantitative and multiplexed detection of proteins from pinpricks of whole blood. Lab Chip (2010) 1.18

Chemistries for patterning robust DNA microbarcodes enable multiplex assays of cytoplasm proteins from single cancer cells. Chemphyschem (2010) 1.11

T cell heterogeneity: firmly fixed, predominantly plastic or merely malleable? Nat Immunol (2008) 1.02

Articles by these authors

Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N Engl J Med (2011) 45.46

Inhibition of mutated, activated BRAF in metastatic melanoma. N Engl J Med (2010) 36.57

Melanomas acquire resistance to B-RAF(V600E) inhibition by RTK or N-RAS upregulation. Nature (2010) 18.69

Safety and tumor responses with lambrolizumab (anti-PD-1) in melanoma. N Engl J Med (2013) 18.08

Clinical efficacy of a RAF inhibitor needs broad target blockade in BRAF-mutant melanoma. Nature (2010) 16.12

Survival in BRAF V600-mutant advanced melanoma treated with vemurafenib. N Engl J Med (2012) 13.17

RAF inhibitor resistance is mediated by dimerization of aberrantly spliced BRAF(V600E). Nature (2011) 10.77

Tumour micro-environment elicits innate resistance to RAF inhibitors through HGF secretion. Nature (2012) 10.39

Evidence of RNAi in humans from systemically administered siRNA via targeted nanoparticles. Nature (2010) 10.09

Pembrolizumab versus Ipilimumab in Advanced Melanoma. N Engl J Med (2015) 8.64

Widespread potential for growth-factor-driven resistance to anticancer kinase inhibitors. Nature (2012) 8.13

Systems biology and new technologies enable predictive and preventative medicine. Science (2004) 7.59

RAS mutations in cutaneous squamous-cell carcinomas in patients treated with BRAF inhibitors. N Engl J Med (2012) 6.93

Improved overall survival in melanoma with combined dabrafenib and trametinib. N Engl J Med (2014) 5.65

Differential sensitivity of melanoma cell lines with BRAFV600E mutation to the specific Raf inhibitor PLX4032. J Transl Med (2010) 5.57

Combined vemurafenib and cobimetinib in BRAF-mutated melanoma. N Engl J Med (2014) 5.43

Melanoma whole-exome sequencing identifies (V600E)B-RAF amplification-mediated acquired B-RAF inhibitor resistance. Nat Commun (2012) 4.94

PTEN loss confers BRAF inhibitor resistance to melanoma cells through the suppression of BIM expression. Cancer Res (2011) 4.80

Silicon nanowires as efficient thermoelectric materials. Nature (2008) 4.80

Combined BRAF and MEK inhibition versus BRAF inhibition alone in melanoma. N Engl J Med (2014) 4.71

Tumor immunotherapy directed at PD-1. N Engl J Med (2012) 4.43

Integrated barcode chips for rapid, multiplexed analysis of proteins in microliter quantities of blood. Nat Biotechnol (2008) 4.40

Highly ordered nanowire arrays on plastic substrates for ultrasensitive flexible chemical sensors. Nat Mater (2007) 3.82

Hepatotoxicity with combination of vemurafenib and ipilimumab. N Engl J Med (2013) 3.51

Multistep synthesis of a radiolabeled imaging probe using integrated microfluidics. Science (2005) 2.83

Nanotechnologies for biomolecular detection and medical diagnostics. Curr Opin Chem Biol (2006) 2.74

Response of BRAF-mutant melanoma to BRAF inhibition is mediated by a network of transcriptional regulators of glycolysis. Cancer Discov (2014) 2.74

HMGB1 mediates endogenous TLR2 activation and brain tumor regression. PLoS Med (2009) 2.56

The AMPK agonist AICAR inhibits the growth of EGFRvIII-expressing glioblastomas by inhibiting lipogenesis. Proc Natl Acad Sci U S A (2009) 2.55

Phase I/II trial of tremelimumab in patients with metastatic melanoma. J Clin Oncol (2009) 2.53

Pharmacodynamic effects and mechanisms of resistance to vemurafenib in patients with metastatic melanoma. J Clin Oncol (2013) 2.51

BRAF(L597) mutations in melanoma are associated with sensitivity to MEK inhibitors. Cancer Discov (2012) 2.48

A 160-kilobit molecular electronic memory patterned at 10(11) bits per square centimetre. Nature (2007) 2.48

Phase II study of the MEK1/MEK2 inhibitor Trametinib in patients with metastatic BRAF-mutant cutaneous melanoma previously treated with or without a BRAF inhibitor. J Clin Oncol (2012) 2.45

DNA-encoded antibody libraries: a unified platform for multiplexed cell sorting and detection of genes and proteins. J Am Chem Soc (2007) 2.42

Combinatorial treatments that overcome PDGFRβ-driven resistance of melanoma cells to V600EB-RAF inhibition. Cancer Res (2011) 2.42

Defining the critical hurdles in cancer immunotherapy. J Transl Med (2011) 2.32

The HSP90 inhibitor XL888 overcomes BRAF inhibitor resistance mediated through diverse mechanisms. Clin Cancer Res (2012) 2.31

Host immunity contributes to the anti-melanoma activity of BRAF inhibitors. J Clin Invest (2013) 2.30

Preexisting MEK1 exon 3 mutations in V600E/KBRAF melanomas do not confer resistance to BRAF inhibitors. Cancer Discov (2012) 2.27

Quantitative real-time measurements of DNA hybridization with alkylated nonoxidized silicon nanowires in electrolyte solution. J Am Chem Soc (2006) 2.22

Marked, homogeneous, and early [18F]fluorodeoxyglucose-positron emission tomography responses to vemurafenib in BRAF-mutant advanced melanoma. J Clin Oncol (2012) 2.21

Electrostatic control of ions and molecules in nanofluidic transistors. Nano Lett (2005) 2.21

BRAF inhibitor vemurafenib improves the antitumor activity of adoptive cell immunotherapy. Cancer Res (2012) 2.14

Phase II trial (BREAK-2) of the BRAF inhibitor dabrafenib (GSK2118436) in patients with metastatic melanoma. J Clin Oncol (2013) 2.13

Graphene visualizes the first water adlayers on mica at ambient conditions. Science (2010) 2.09

Controlled growth of Si nanowire arrays for device integration. Nano Lett (2005) 2.02

The oncogenic BRAF kinase inhibitor PLX4032/RG7204 does not affect the viability or function of human lymphocytes across a wide range of concentrations. Clin Cancer Res (2010) 2.02

Ultrahigh-density nanowire lattices and circuits. Science (2003) 2.01

Targeted therapy resistance mediated by dynamic regulation of extrachromosomal mutant EGFR DNA. Science (2013) 2.00

Reversing melanoma cross-resistance to BRAF and MEK inhibitors by co-targeting the AKT/mTOR pathway. PLoS One (2011) 1.89

Determinant spreading associated with clinical response in dendritic cell-based immunotherapy for malignant melanoma. Clin Cancer Res (2003) 1.83

The TLR-7 agonist, imiquimod, enhances dendritic cell survival and promotes tumor antigen-specific T cell priming: relation to central nervous system antitumor immunity. J Immunol (2006) 1.79

A systematic approach to biomarker discovery; preamble to "the iSBTc-FDA taskforce on immunotherapy biomarkers". J Transl Med (2008) 1.77

Single-cell proteomic chip for profiling intracellular signaling pathways in single tumor cells. Proc Natl Acad Sci U S A (2011) 1.76

Migration to apoptotic "find-me" signals is mediated via the phagocyte receptor G2A. J Biol Chem (2007) 1.75

A novel AKT1 mutant amplifies an adaptive melanoma response to BRAF inhibition. Cancer Discov (2013) 1.75

Combined immunostimulation and conditional cytotoxic gene therapy provide long-term survival in a large glioma model. Cancer Res (2005) 1.74

Regulation of cyclin dependent kinase 6 by microRNA 124 in medulloblastoma. J Neurooncol (2008) 1.72

Reduction of thermal conductivity in phononic nanomesh structures. Nat Nanotechnol (2010) 1.70

Multifunctional T-cell analyses to study response and progression in adoptive cell transfer immunotherapy. Cancer Discov (2013) 1.68

CTLA4 blockade broadens the peripheral T-cell receptor repertoire. Clin Cancer Res (2014) 1.66

Iterative in situ click chemistry creates antibody-like protein-capture agents. Angew Chem Int Ed Engl (2009) 1.64

Antitumor activity from antigen-specific CD8 T cells generated in vivo from genetically engineered human hematopoietic stem cells. Proc Natl Acad Sci U S A (2011) 1.61

T-cell responses to survivin in cancer patients undergoing radiation therapy. Clin Cancer Res (2008) 1.61

Antitumor activity of the ERK inhibitor SCH772984 [corrected] against BRAF mutant, NRAS mutant and wild-type melanoma. Mol Cancer (2014) 1.59

Piezoelectric ribbons printed onto rubber for flexible energy conversion. Nano Lett (2010) 1.57

Detailed analysis of immunologic effects of the cytotoxic T lymphocyte-associated antigen 4-blocking monoclonal antibody tremelimumab in peripheral blood of patients with melanoma. J Transl Med (2008) 1.56