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Artikel ; Online: Silencing stemness in T cell differentiation.

Henning, Amanda N / Klebanoff, Christopher A / Restifo, Nicholas P

2019 Band 359, Heft 6372, Seite(n) 163–164

Mesh-Begriff(e)	Cell Differentiation ; Humans ; Neoplastic Stem Cells
Sprache	Englisch
Erscheinungsdatum	2019-01-02
Erscheinungsland	United States
Dokumenttyp	Journal Article ; Comment
ZDB-ID	128410-1
ISSN	1095-9203 ; 0036-8075
ISSN (online)	1095-9203
ISSN	0036-8075
DOI	10.1126/science.aar5541
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Epigenetic control of CD8

Henning, Amanda N / Roychoudhuri, Rahul / Restifo, Nicholas P

Nature reviews. Immunology

2018 Band 18, Heft 5, Seite(n) 340–356

Abstract: Upon stimulation, small numbers of naive ... ...

Abstract	Upon stimulation, small numbers of naive CD8
Mesh-Begriff(e)	Animals ; CD8-Positive T-Lymphocytes/cytology ; CD8-Positive T-Lymphocytes/immunology ; CD8-Positive T-Lymphocytes/metabolism ; Cell Differentiation/genetics ; Cell Differentiation/immunology ; Cellular Reprogramming Techniques/methods ; Chromatin Assembly and Disassembly/genetics ; Chromatin Assembly and Disassembly/immunology ; DNA Methylation/immunology ; Enhancer Elements, Genetic ; Epigenesis, Genetic/immunology ; Histone Code/genetics ; Humans ; Immunotherapy/methods ; Models, Genetic ; Models, Immunological ; Transcription, Genetic
Sprache	Englisch
Erscheinungsdatum	2018-01-30
Erscheinungsland	England
Dokumenttyp	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2062776-2
ISSN	1474-1741 ; 1474-1733
ISSN (online)	1474-1741
ISSN	1474-1733
DOI	10.1038/nri.2017.146
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Immunomagnetic B cell isolation as a tool to study blood cell subsets and enrich B cell transcripts.

Henning, Amanda N / Green, Daniel / Baumann, Ryan / Grandinetti, Patrick / Highfill, Steven L / Zhou, Huizhi / De Giorgi, Valeria

BMC research notes

2021 Band 14, Heft 1, Seite(n) 418

Abstract: Objective: Transcriptional profiling of immune cells is an indispensable tool in biomedical research; however, heterogenous sample types routinely used in transcriptomic studies may mask important cell type-specific transcriptional differences. ... ...

Abstract	Objective: Transcriptional profiling of immune cells is an indispensable tool in biomedical research; however, heterogenous sample types routinely used in transcriptomic studies may mask important cell type-specific transcriptional differences. Techniques to isolate desired cell types are used to overcome this limitation. We sought to evaluate the use of immunomagnetic B cell isolation on RNA quality and transcriptional output. Additionally, we aimed to develop a B cell gene signature representative of a freshly isolated B cell population to be used as a tool to verify isolation efficacy and to provide a transcriptional standard for evaluating maintenance or deviation from traditional B cell identity. Results: We found RNA quality and RNA-sequencing output to be comparable between donor-matched PBMC, whole blood, and B cells following negative selection by immunomagnetic B cell isolation. Transcriptional analysis enabled the development of an 85 gene B cell signature. This signature effectively clustered isolated B cells from heterogeneous sample types in our study and naïve and memory B cells when applied to transcriptional data from a published source. Additionally, by identifying B cell signature genes whose functional role in B cells is currently unknown, our gene signature has uncovered areas for future investigation.
Mesh-Begriff(e)	B-Lymphocytes ; Cell Separation ; Gene Expression Profiling ; Leukocytes, Mononuclear ; RNA ; Transcriptome
Chemische Substanzen	RNA (63231-63-0)
Sprache	Englisch
Erscheinungsdatum	2021-11-18
Erscheinungsland	England
Dokumenttyp	Journal Article
ZDB-ID	2413336-X
ISSN	1756-0500 ; 1756-0500
ISSN (online)	1756-0500
ISSN	1756-0500
DOI	10.1186/s13104-021-05833-z
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel: Anti-SARS-CoV-2 Serology persistence over time in COVID-19 Convalescent Plasma Donors.

De Giorgi, Valeria / West, Kamille A / Henning, Amanda N / Chen, Leonard / Holbrook, Michael R / Gross, Robin / Liang, Janie / Postnikova, Elena / Trenbeath, Joni / Pogue, Sarah / Scinto, Tania / Alter, Harvey J / Cantilena, Cathy Corny

medRxiv : the preprint server for health sciences

2021

Abstract: Background: Characterizing the kinetics of the antibody response to SARS□CoV□2 is of critical importance to developing strategies that may mitigate the public health burden of COVID-19. We sought to determine how circulating antibody levels change over ... ...

Abstract	Background: Characterizing the kinetics of the antibody response to SARS□CoV□2 is of critical importance to developing strategies that may mitigate the public health burden of COVID-19. We sought to determine how circulating antibody levels change over time following natural infection. Methods/materials: We conducted a prospective, longitudinal analysis of COVID-19 convalescent plasma (CCP) donors at multiple time points over a 9-month period. At each study visit, subjects either donated plasma or only had study samples drawn. In all cases, anti-SARS-CoV-2 donor testing was performed using semi-quantitative chemiluminescent immunoassays (ChLIA) targeting subunit 1 (S1) of the SARS-CoV-2 spike (S) protein, and an in-house fluorescence reduction neutralization assay (FRNA). Results: From April to November 2020 we enrolled 202 donors, mean age 47.3 ±14.7 years, 55% female, 75% Caucasian. Most donors reported a mild clinical course (91%, n=171) without hospitalization. One hundred and five (105) (52%) donors presented for repeat visits with a median 42 (12-163) days between visits. The final visit occurred at a median 160 (53-273) days post-symptom resolution. Total anti-SARS-CoV-2 antibodies (Ab), SARS-CoV-2 specific IgG and neutralizing antibodies were detected in 97.5%, 91.1%, and 74% of donors respectively at initial presentation. Neutralizing Ab titers based on FRNA Conclusion: Anti-SARS-CoV-2 antibodies were identified in 97% of convalescent donors at initial presentation. In a cohort that largely did not require hospitalization. IgG and neutralizing antibodies were positively correlated with age, BMI and clinical severity, and persisted for up to 9 months post-recovery from natural infection. On repeat presentation, IgG anti-SARS-CoV-2 levels decreased in 56% of repeat donors. Overall, these data suggest that CP donors possess a wide range of IgG and neutralizing antibody levels that are proportionally distributed across demographics, with the exception of age, BMI and clinical severity.
Sprache	Englisch
Erscheinungsdatum	2021-03-10
Erscheinungsland	United States
Dokumenttyp	Preprint
DOI	10.1101/2021.03.08.21253093
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Naturally Acquired SARS-CoV-2 Immunity Persists for Up to 11 Months Following Infection.

De Giorgi, Valeria / West, Kamille A / Henning, Amanda N / Chen, Leonard N / Holbrook, Michael R / Gross, Robin / Liang, Janie / Postnikova, Elena / Trenbeath, Joni / Pogue, Sarah / Scinto, Tania / Alter, Harvey J / Cantilena, Cathy Conry

The Journal of infectious diseases

2021 Band 224, Heft 8, Seite(n) 1294–1304

Abstract: Background: Characterizing the kinetics of the antibody response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is of critical importance to developing strategies that may mitigate the public health burden of coronavirus disease 2019 ( ... ...

Abstract	Background: Characterizing the kinetics of the antibody response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is of critical importance to developing strategies that may mitigate the public health burden of coronavirus disease 2019 (COVID-19). We conducted a prospective, longitudinal analysis of COVID-19 convalescent plasma donors at multiple time points over an 11-month period to determine how circulating antibody levels change over time following natural infection. Methods: From April 2020 to February 2021, we enrolled 228 donors. At each study visit, subjects either donated plasma or had study samples drawn only. Anti-SARS-CoV-2 donor testing was performed using the VITROS Anti-SARS-CoV-2 Total and IgG assays and an in-house fluorescence reduction neutralization assay. Results: Anti-SARS-CoV-2 antibodies were identified in 97% of COVID-19 convalescent donors at initial presentation. In follow-up analyses, of 116 donors presenting at repeat time points, 91.4% had detectable IgG levels up to 11 months after symptom recovery, while 63% had detectable neutralizing titers; however, 25% of donors had neutralizing levels that dropped to an undetectable titer over time. Conclusions: Our data suggest that immunological memory is acquired in most individuals infected with SARS-CoV-2 and is sustained in a majority of patients for up to 11 months after recovery. Clinical Trials Registration. NCT04360278.
Mesh-Begriff(e)	Adaptive Immunity ; Adolescent ; Adult ; Aged ; Antibodies, Neutralizing/blood ; Antibodies, Neutralizing/immunology ; Antibodies, Viral/blood ; Antibodies, Viral/immunology ; COVID-19/blood ; COVID-19/diagnosis ; COVID-19/immunology ; COVID-19/virology ; Convalescence ; Female ; Humans ; Longitudinal Studies ; Male ; Middle Aged ; Prospective Studies ; SARS-CoV-2/immunology ; SARS-CoV-2/isolation & purification ; Time Factors ; Young Adult
Chemische Substanzen	Antibodies, Neutralizing ; Antibodies, Viral
Sprache	Englisch
Erscheinungsdatum	2021-06-05
Erscheinungsland	United States
Dokumenttyp	Journal Article ; Observational Study ; Research Support, N.I.H., Intramural ; Research Support, Non-U.S. Gov't
ZDB-ID	3019-3
ISSN	1537-6613 ; 0022-1899
ISSN (online)	1537-6613
ISSN	0022-1899
DOI	10.1093/infdis/jiab295
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: The Non-coding Mammary Carcinoma Susceptibility Locus, Mcs5c, Regulates Pappa Expression via Age-Specific Chromatin Folding and Allele-Dependent DNA Methylation.

Henning, Amanda N / Haag, Jill D / Smits, Bart M G / Gould, Michael N

PLoS genetics

2016 Band 12, Heft 8, Seite(n) e1006261

Abstract: In understanding the etiology of breast cancer, the contributions of both genetic and environmental risk factors are further complicated by the impact of breast developmental stage. Specifically, the time period ranging from childhood to young adulthood ... ...

Abstract	In understanding the etiology of breast cancer, the contributions of both genetic and environmental risk factors are further complicated by the impact of breast developmental stage. Specifically, the time period ranging from childhood to young adulthood represents a critical developmental window in a woman's life when she is more susceptible to environmental hazards that may affect future breast cancer risk. Although the effects of environmental exposures during particular developmental Windows of Susceptibility (WOS) are well documented, the genetic mechanisms governing these interactions are largely unknown. Functional characterization of the Mammary Carcinoma Susceptibility 5c, Mcs5c, congenic rat model of breast cancer at various stages of mammary gland development was conducted to gain insight into the interplay between genetic risk factors and WOS. Using quantitative real-time PCR, chromosome conformation capture, and bisulfite pyrosequencing we have found that Mcs5c acts within the mammary gland to regulate expression of the neighboring gene Pappa during a critical mammary developmental time period in the rat, corresponding to the human young adult WOS. Pappa has been shown to positively regulate the IGF signaling pathway, which is required for proper mammary gland/breast development and is of increasing interest in breast cancer pathogenesis. Mcs5c-mediated regulation of Pappa appears to occur through age-dependent and mammary gland-specific chromatin looping, as well as genotype-dependent CpG island shore methylation. This represents, to our knowledge, the first insight into cellular mechanisms underlying the WOS phenomenon and demonstrates the influence developmental stage can have on risk locus functionality. Additionally, this work represents a novel model for further investigation into how environmental factors, together with genetic factors, modulate breast cancer risk in the context of breast developmental stage.
Mesh-Begriff(e)	Animals ; Breast Neoplasms/genetics ; Breast Neoplasms/pathology ; Chromatin/genetics ; CpG Islands/genetics ; DNA Methylation/genetics ; Disease Models, Animal ; Female ; Gene Expression Regulation, Neoplastic ; Genetic Predisposition to Disease ; Humans ; Mammary Glands, Human/pathology ; Mammary Neoplasms, Experimental/genetics ; Mammary Neoplasms, Experimental/pathology ; Quantitative Trait Loci/genetics ; Rats ; Signal Transduction ; Somatomedins/genetics
Chemische Substanzen	Chromatin ; Somatomedins
Sprache	Englisch
Erscheinungsdatum	2016-08-18
Erscheinungsland	United States
Dokumenttyp	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, N.I.H., Extramural
ZDB-ID	2186725-2
ISSN	1553-7404 ; 1553-7390
ISSN (online)	1553-7404
ISSN	1553-7390
DOI	10.1371/journal.pgen.1006261
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Cancer genes disfavoring T cell immunity identified via integrated systems approach.

Cell reports

2022 Band 40, Heft 5, Seite(n) 111153

Abstract: Adoptive T cell therapies (ACT) have been curative for a limited number of cancer patients. The sensitization of cancer cells to T cell killing may expand the benefit of these therapies for more patients. To this end, we use a three-step approach to ... ...

Abstract	Adoptive T cell therapies (ACT) have been curative for a limited number of cancer patients. The sensitization of cancer cells to T cell killing may expand the benefit of these therapies for more patients. To this end, we use a three-step approach to identify cancer genes that disfavor T cell immunity. First, we profile gene transcripts upregulated by cancer under selection pressure from T cell killing. Second, we identify potential tumor gene targets and pathways that disfavor T cell killing using signaling pathway activation libraries and genome-wide loss-of-function CRISPR-Cas9 screens. Finally, we implement pharmacological perturbation screens to validate these targets and identify BIRC2, ITGAV, DNPEP, BCL2, and ERRα as potential ACT-drug combination candidates. Here, we establish that BIRC2 limits antigen presentation and T cell recognition of tumor cells by suppressing IRF1 activity and provide evidence that BIRC2 inhibition in combination with ACT is an effective strategy to increase efficacy.
Mesh-Begriff(e)	Antigen Presentation ; CRISPR-Cas Systems/genetics ; Humans ; Neoplasms/genetics ; Oncogenes ; Systems Analysis ; T-Lymphocytes
Sprache	Englisch
Erscheinungsdatum	2022-08-04
Erscheinungsland	United States
Dokumenttyp	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Intramural ; Research Support, N.I.H., Extramural
ZDB-ID	2649101-1
ISSN	2211-1247 ; 2211-1247
ISSN (online)	2211-1247
ISSN	2211-1247
DOI	10.1016/j.celrep.2022.111153
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Anti-SARS-CoV-2 Serology persistence over time in COVID-19 Convalescent Plasma Donors.

medRxiv

Abstract: Background: Characterizing the kinetics of the antibody response to SARS-CoV-2 is of critical importance to developing strategies that may mitigate the public health burden of COVID-19. We sought to determine how circulating antibody levels change over ... ...

Abstract	Background: Characterizing the kinetics of the antibody response to SARS-CoV-2 is of critical importance to developing strategies that may mitigate the public health burden of COVID-19. We sought to determine how circulating antibody levels change over time following natural infection. Methods/Materials: We conducted a prospective, longitudinal analysis of COVID-19 convalescent plasma (CCP) donors at multiple time points over a 9-month period. At each study visit, subjects either donated plasma or only had study samples drawn. In all cases, anti-SARS-CoV-2 donor testing was performed using semi-quantitative chemiluminescent immunoassays (ChLIA) targeting subunit 1 (S1) of the SARS-CoV-2 spike (S) protein, and an in-house fluorescence reduction neutralization assay (FRNA). Results: From April to November 2020 we enrolled 202 donors, mean age 47.3 +/- 14.7 years, 55% female, 75% Caucasian. Most donors reported a mild clinical course (91%, n=171) without hospitalization. One hundred and five (105) (52%) donors presented for repeat visits with a median 42 (12 -163) days between visits. The final visit occurred at a median 160 (53-273) days post-symptom resolution. Total anti-SARS-CoV-2 antibodies (Ab), SARS-CoV-2 specific IgG and neutralizing antibodies were detected in 97.5%, 91.1%, and 74% of donors respectively at initial presentation. Neutralizing Ab titers based on FRNA50 were positively associated with mean IgG levels (p = <0.0001). Mean IgG levels and neutralizing titers were positively associated with COVID-19 severity, increased donor age and BMI (p=0.0006 and p=0.0028, p=0.0083 and p=0.0363, (p=0.0008 and p=0.0018, respectively). Over the course of repeat visits, IgG decreased in 74.1% of donors; FRNA50 decreased in 44.4% and remained unchanged in 33.3% of repeat donors. A weak negative correlation was observed between total Ab levels and number of days post-symptom recovery (r = 0.09). Conclusion: Anti-SARS-CoV-2 antibodies were identified in 97% of convalescent donors at initial presentation. In a cohort that largely did not require hospitalization. IgG and neutralizing antibodies were positively correlated with age, BMI and clinical severity, and persisted for up to 9 months post-recovery from natural infection. On repeat presentation, IgG anti-SARS-CoV-2 levels decreased in 56% of repeat donors. Overall, these data suggest that CP donors possess a wide range of IgG and neutralizing antibody levels that are proportionally distributed across demographics, with the exception of age, BMI and clinical severity.
Schlagwörter	covid19
Sprache	Englisch
Erscheinungsdatum	2021-03-10
Verlag	Cold Spring Harbor Laboratory Press
Dokumenttyp	Artikel ; Online
DOI	10.1101/2021.03.08.21253093
Datenquelle	COVID19

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Artikel ; Online: Multi-phenotype CRISPR-Cas9 Screen Identifies p38 Kinase as a Target for Adoptive Immunotherapies.

Gurusamy, Devikala / Henning, Amanda N / Yamamoto, Tori N / Yu, Zhiya / Zacharakis, Nikolaos / Krishna, Sri / Kishton, Rigel J / Vodnala, Suman K / Eidizadeh, Arash / Jia, Li / Kariya, Christine M / Black, Mary A / Eil, Robert / Palmer, Douglas C / Pan, Jenny H / Sukumar, Madhusudhanan / Patel, Shashank J / Restifo, Nicholas P

Cancer cell

2020 Band 37, Heft 6, Seite(n) 818–833.e9

Abstract: T cells are central to all currently effective cancer immunotherapies, but the characteristics defining therapeutically effective anti-tumor T cells have not been comprehensively elucidated. Here, we delineate four phenotypic qualities of effective anti- ... ...

Abstract	T cells are central to all currently effective cancer immunotherapies, but the characteristics defining therapeutically effective anti-tumor T cells have not been comprehensively elucidated. Here, we delineate four phenotypic qualities of effective anti-tumor T cells: cell expansion, differentiation, oxidative stress, and genomic stress. Using a CRISPR-Cas9-based genetic screen of primary T cells we measured the multi-phenotypic impact of disrupting 25 T cell receptor-driven kinases. We identified p38 kinase as a central regulator of all four phenotypes and uncovered transcriptional and antioxidant pathways regulated by p38 in T cells. Pharmacological inhibition of p38 improved the efficacy of mouse anti-tumor T cells and enhanced the functionalities of human tumor-reactive and gene-engineered T cells, paving the way for clinically relevant interventions.
Mesh-Begriff(e)	Animals ; Breast Neoplasms/immunology ; Breast Neoplasms/pathology ; Breast Neoplasms/therapy ; CRISPR-Cas Systems ; Cell Differentiation ; Female ; Genetic Engineering ; Immunotherapy, Adoptive/methods ; Male ; Melanoma, Experimental/immunology ; Melanoma, Experimental/pathology ; Melanoma, Experimental/therapy ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Phenotype ; Receptors, Antigen, T-Cell/physiology ; T-Lymphocytes/immunology ; T-Lymphocytes/transplantation ; p38 Mitogen-Activated Protein Kinases/antagonists & inhibitors ; p38 Mitogen-Activated Protein Kinases/genetics
Chemische Substanzen	Receptors, Antigen, T-Cell ; p38 Mitogen-Activated Protein Kinases (EC 2.7.11.24)
Sprache	Englisch
Erscheinungsdatum	2020-08-11
Erscheinungsland	United States
Dokumenttyp	Journal Article ; Research Support, N.I.H., Intramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2078448-X
ISSN	1878-3686 ; 1535-6108
ISSN (online)	1878-3686
ISSN	1535-6108
DOI	10.1016/j.ccell.2020.05.004
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Host conditioning with IL-1β improves the antitumor function of adoptively transferred T cells.

Lee, Ping-Hsien / Yamamoto, Tori N / Gurusamy, Devikala / Sukumar, Madhusudhanan / Yu, Zhiya / Hu-Li, Jane / Kawabe, Takeshi / Gangaplara, Arunakumar / Kishton, Rigel J / Henning, Amanda N / Vodnala, Suman K / Germain, Ronald N / Paul, William E / Restifo, Nicholas P

The Journal of experimental medicine

2019 Band 216, Heft 11, Seite(n) 2619–2634

Abstract: Host conditioning has emerged as an important component of effective adoptive cell transfer-based immunotherapy for cancer. High levels of IL-1β are induced by host conditioning, but its impact on the antitumor function of T cells remains unclear. We ... ...

Abstract	Host conditioning has emerged as an important component of effective adoptive cell transfer-based immunotherapy for cancer. High levels of IL-1β are induced by host conditioning, but its impact on the antitumor function of T cells remains unclear. We found that the administration of IL-1β increased the population size and functionality of adoptively transferred T cells within the tumor. Most importantly, IL-1β enhanced the ability of tumor-specific T cells to trigger the regression of large, established B16 melanoma tumors in mice. Mechanistically, we showed that the increase in T cell numbers was associated with superior tissue homing and survival abilities and was largely mediated by IL-1β-stimulated host cells. In addition, IL-1β enhanced T cell functionality indirectly via its actions on radio-resistant host cells in an IL-2- and IL-15-dependent manner. Our findings not only underscore the potential of provoking inflammation to enhance antitumor immunity but also uncover novel host regulations of T cell responses.
Mesh-Begriff(e)	Adoptive Transfer ; Animals ; Cell Line, Tumor ; Cytokines/blood ; Immunotherapy, Adoptive/methods ; Interleukin-1beta/immunology ; Interleukin-1beta/metabolism ; Interleukin-6/blood ; Lymphocyte Activation/immunology ; Melanoma, Experimental/immunology ; Melanoma, Experimental/metabolism ; Melanoma, Experimental/therapy ; Mice, Inbred C57BL ; Mice, Knockout ; Mice, Transgenic ; T-Lymphocytes/immunology ; T-Lymphocytes/metabolism ; T-Lymphocytes/transplantation ; Tumor Necrosis Factor-alpha/blood
Chemische Substanzen	Cytokines ; Interleukin-1beta ; Interleukin-6 ; Tumor Necrosis Factor-alpha
Sprache	Englisch
Erscheinungsdatum	2019-08-12
Erscheinungsland	United States
Dokumenttyp	Journal Article ; Research Support, N.I.H., Intramural ; Research Support, Non-U.S. Gov't
ZDB-ID	218343-2
ISSN	1540-9538 ; 0022-1007
ISSN (online)	1540-9538
ISSN	0022-1007
DOI	10.1084/jem.20181218
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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