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  1. Article ; Online: Tsyn-Seq: a T-cell Synapse-Based Antigen Identification Platform.

    Jin, Yimei / Miyama, Takahiko / Brown, Alexandria / Hayase, Tomo / Song, Xingzhi / Singh, Anand K / Huang, Licai / Flores, Ivonne I / McDaniel, Lauren K / Glover, Israel / Halsey, Taylor M / Prasad, Rishika / Chapa, Valerie / Ahmed, Saira / Zhang, Jianhua / Rai, Kunal / Peterson, Christine B / Lizee, Gregory / Karmouch, Jennifer /
    Hayase, Eiko / Molldrem, Jeffrey J / Chang, Chia-Chi / Tsai, Wen-Bin / Jenq, Robert R

    Cancer immunology research

    2024  Volume 12, Issue 5, Page(s) 530–543

    Abstract: Tools for genome-wide rapid identification of peptide-major histocompatibility complex targets of T-cell receptors (TCR) are not yet universally available. We present a new antigen screening method, the T-synapse (Tsyn) reporter system, which includes ... ...

    Abstract Tools for genome-wide rapid identification of peptide-major histocompatibility complex targets of T-cell receptors (TCR) are not yet universally available. We present a new antigen screening method, the T-synapse (Tsyn) reporter system, which includes antigen-presenting cells (APC) with a Fas-inducible NF-κB reporter and T cells with a nuclear factor of activated T cells (NFAT) reporter. To functionally screen for target antigens from a cDNA library, productively interacting T cell-APC aggregates were detected by dual-reporter activity and enriched by flow sorting followed by antigen identification quantified by deep sequencing (Tsyn-seq). When applied to a previously characterized TCR specific for the E7 antigen derived from human papillomavirus type 16 (HPV16), Tsyn-seq successfully enriched the correct cognate antigen from a cDNA library derived from an HPV16-positive cervical cancer cell line. Tsyn-seq provides a method for rapidly identifying antigens recognized by TCRs of interest from a tumor cDNA library. See related Spotlight by Makani and Joglekar, p. 515.
    MeSH term(s) Humans ; Receptors, Antigen, T-Cell/immunology ; Receptors, Antigen, T-Cell/genetics ; T-Lymphocytes/immunology ; High-Throughput Nucleotide Sequencing ; Papillomavirus E7 Proteins/immunology ; Papillomavirus E7 Proteins/genetics ; Gene Library ; Antigen-Presenting Cells/immunology ; NFATC Transcription Factors/metabolism ; NFATC Transcription Factors/immunology ; Cell Line, Tumor ; NF-kappa B/metabolism ; Immunological Synapses/immunology ; Human papillomavirus 16/immunology ; Human papillomavirus 16/genetics ; Female
    Chemical Substances Receptors, Antigen, T-Cell ; Papillomavirus E7 Proteins ; NFATC Transcription Factors ; oncogene protein E7, Human papillomavirus type 16 ; NF-kappa B
    Language English
    Publishing date 2024-02-16
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 2732489-8
    ISSN 2326-6074 ; 2326-6066
    ISSN (online) 2326-6074
    ISSN 2326-6066
    DOI 10.1158/2326-6066.CIR-23-0467
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 7022: Show issues Location:
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  2. Article ; Online: Oncolytic HSV Therapy Modulates Vesicular Trafficking Inducing Cisplatin Sensitivity and Antitumor Immunity.

    Hong, Bangxing / Chapa, Valerie / Saini, Uksha / Modgil, Puneet / Cohn, David E / He, Guangan / Siddik, Zahid H / Sood, Anil K / Yan, Yuanqing / Selvendiran, Karuppaiyah / Pei, Guangsheng / Zhao, Zhongming / Yoo, Ji Young / Kaur, Balveen

    Clinical cancer research : an official journal of the American Association for Cancer Research

    2020  Volume 27, Issue 2, Page(s) 542–553

    Abstract: Purpose: Here we investigated the impact of oncolytic herpes simplex virus (HSV) treatment on cisplatin sensitivity of platinum-resistant ovarian cancer, and the impact of the combination on immunotherapy.: Experimental design: Therapeutic efficacy ... ...

    Abstract Purpose: Here we investigated the impact of oncolytic herpes simplex virus (HSV) treatment on cisplatin sensitivity of platinum-resistant ovarian cancer, and the impact of the combination on immunotherapy.
    Experimental design: Therapeutic efficacy of the combination was assessed in platinum-resistant human and murine ovarian cancer peritoneal metastatic mouse models (
    Results: Gene Ontology pathway analysis uncovered disruption of cellular extracellular vesicle (EV)-related pathways in infected cells (FDR = 2.97E-57). Mechanistically, we identified reduced expression of transporters expressed on EV implicated in cisplatin efflux. The increased cisplatin retention led to increased cisplatin-DNA adducts, which resulted in micronuclei and the subsequent activation of cGAS-STING pathway with a significant activation of innate immune cells and translated to an increase in antitumor immunity and efficacy. In mice bearing platinum-resistant ovarian cancer, we also observed a feedback induction of PD-L1 on tumor cells, which sensitized combination-treated mice to anti-PD-1 immune checkpoint therapy.
    Conclusions: To our knowledge, this is the first report to show HSV-induced cisplatin retention in infected cells. The consequential increased damaged DNA was then expelled from cells as micronuclei which resulted in induction of inflammatory responses and education of antitumor immunity. The combination therapy also created an environment that sensitized tumors to immune checkpoint therapy.
    MeSH term(s) Animals ; Antineoplastic Agents/therapeutic use ; Cell Line, Tumor ; Cells, Cultured ; Cisplatin/therapeutic use ; Combined Modality Therapy ; DNA Adducts/genetics ; DNA Adducts/immunology ; Disease Models, Animal ; Female ; Herpesvirus 1, Human/physiology ; Humans ; Immunotherapy/methods ; Mice, Inbred C57BL ; Mice, Inbred NOD ; Mice, Knockout ; Mice, SCID ; Oncolytic Virotherapy/methods ; Ovarian Neoplasms/genetics ; Ovarian Neoplasms/therapy ; Ovarian Neoplasms/virology ; Signal Transduction/genetics ; Signal Transduction/immunology ; Treatment Outcome ; Xenograft Model Antitumor Assays/methods ; Mice
    Chemical Substances Antineoplastic Agents ; DNA Adducts ; Cisplatin (Q20Q21Q62J)
    Language English
    Publishing date 2020-10-21
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 1225457-5
    ISSN 1557-3265 ; 1078-0432
    ISSN (online) 1557-3265
    ISSN 1078-0432
    DOI 10.1158/1078-0432.CCR-20-2210
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 4223: Show issues Location:
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  3. Article ; Online: Mucus-degrading Bacteroides link carbapenems to aggravated graft-versus-host disease

    Hayase, Eiko / Hayase, Tomo / Jamal, Mohamed A. / Miyama, Takahiko / Chang, Chia-Chi / Ortega, Miriam R. / Ahmed, Saira S. / Karmouch, Jennifer L. / Sanchez, Christopher A. / Brown, Alexandria N. / El-Himri, Rawan K. / Flores, Ivonne I. / McDaniel, Lauren K. / Phạm, Dũng / Halsey, Taylor / Frenk, Annette C. / Chapa, Valerie A. / Heckel, Brooke E. / Jin, Yimei /
    Tsai, Wen-Bin / Prasad, Rishika / Tan, Lin / Veillon, Lucas / Ajami, Nadim J. / Wargo, Jennifer A. / Galloway-Peña, Jessica / Shelburne, Samuel / Chemaly, Roy F. / Davey, Lauren / Glowacki, Robert W.P. / Liu, Chen / Rondon, Gabriela / Alousi, Amin M. / Molldrem, Jeffrey J. / Champlin, Richard / Shpall, Elizabeth J. / Valdivia, Raphael H. / Martens, Eric C. / Lorenzi, Philip L. / Jenq, Robert R.

    Cell. 2022 Sept. 29, v. 185, no. 20 p.3705-3719.e14

    2022  

    Abstract: The intestinal microbiota is an important modulator of graft-versus-host disease (GVHD), which often complicates allogeneic hematopoietic stem cell transplantation (allo-HSCT). Broad-spectrum antibiotics such as carbapenems increase the risk for ... ...

    Abstract The intestinal microbiota is an important modulator of graft-versus-host disease (GVHD), which often complicates allogeneic hematopoietic stem cell transplantation (allo-HSCT). Broad-spectrum antibiotics such as carbapenems increase the risk for intestinal GVHD, but mechanisms are not well understood. In this study, we found that treatment with meropenem, a commonly used carbapenem, aggravates colonic GVHD in mice via the expansion of Bacteroides thetaiotaomicron (BT). BT has a broad ability to degrade dietary polysaccharides and host mucin glycans. BT in meropenem-treated allogeneic mice demonstrated upregulated expression of enzymes involved in the degradation of mucin glycans. These mice also had thinning of the colonic mucus layer and decreased levels of xylose in colonic luminal contents. Interestingly, oral xylose supplementation significantly prevented thinning of the colonic mucus layer in meropenem-treated mice. Specific nutritional supplementation strategies, including xylose supplementation, may combat antibiotic-mediated microbiome injury to reduce the risk for intestinal GVHD in allo-HSCT patients.
    Keywords Bacteroides thetaiotaomicron ; cell transplantation ; dietary supplements ; hematopoietic stem cells ; intestinal microorganisms ; intestines ; meropenem ; microbiome ; mucins ; mucus ; polysaccharides ; risk ; risk reduction ; xylose ; mucus-degrading bacteria ; Bacteroides ; allogeneic hematopoietic stem cell transplantation ; graft-versus-host disease ; broad-spectrum antibiotics ; carbapenem ; mucus layer ; intestinal microbiome
    Language English
    Dates of publication 2022-0929
    Size p. 3705-3719.e14.
    Publishing place Elsevier Inc.
    Document type Article ; Online
    ZDB-ID 187009-9
    ISSN 1097-4172 ; 0092-8674
    ISSN (online) 1097-4172
    ISSN 0092-8674
    DOI 10.1016/j.cell.2022.09.007
    Database NAL-Catalogue (AGRICOLA)

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  4. Article: Bacteroides ovatus

    Hayase, Eiko / Hayase, Tomo / Mukherjee, Akash / Stinson, Stuart C / Jamal, Mohamed A / Ortega, Miriam R / Sanchez, Christopher A / Ahmed, Saira S / Karmouch, Jennifer L / Chang, Chia-Chi / Flores, Ivonne I / McDaniel, Lauren K / Brown, Alexandria N / El-Himri, Rawan K / Chapa, Valerie A / Tan, Lin / Tran, Bao Q / Pham, Dung / Halsey, Taylor M /
    Jin, Yimei / Tsai, Wen-Bin / Prasad, Rishika / Glover, Israel K / Ajami, Nadim J / Wargo, Jennifer A / Shelburne, Samuel / Okhuysen, Pablo C / Liu, Chen / Fowler, Stephanie W / Conner, Margaret E / Peterson, Christine B / Rondon, Gabriela / Molldrem, Jeffrey J / Champlin, Richard E / Shpall, Elizabeth J / Lorenzi, Philip L / Mehta, Rohtesh S / Martens, Eric C / Alousi, Amin M / Jenq, Robert R

    Research square

    2023  

    Abstract: Acute gastrointestinal intestinal GVHD (aGI-GVHD) is a serious complication of allogeneic hematopoietic stem cell transplantation, and the intestinal microbiota is known to impact on its severity. However, an association between treatment response of aGI- ...

    Abstract Acute gastrointestinal intestinal GVHD (aGI-GVHD) is a serious complication of allogeneic hematopoietic stem cell transplantation, and the intestinal microbiota is known to impact on its severity. However, an association between treatment response of aGI-GVHD and the intestinal microbiota has not been well-studied. In a cohort of patients with aGI-GVHD (n=37), we found that non-response to standard therapy with corticosteroids was associated with prior treatment with carbapenem antibiotics and loss of
    Language English
    Publishing date 2023-01-31
    Publishing country United States
    Document type Preprint
    DOI 10.21203/rs.3.rs-2460097/v1
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Mucus-degrading Bacteroides link carbapenems to aggravated graft-versus-host disease.

    Hayase, Eiko / Hayase, Tomo / Jamal, Mohamed A / Miyama, Takahiko / Chang, Chia-Chi / Ortega, Miriam R / Ahmed, Saira S / Karmouch, Jennifer L / Sanchez, Christopher A / Brown, Alexandria N / El-Himri, Rawan K / Flores, Ivonne I / McDaniel, Lauren K / Pham, Dung / Halsey, Taylor / Frenk, Annette C / Chapa, Valerie A / Heckel, Brooke E / Jin, Yimei /
    Tsai, Wen-Bin / Prasad, Rishika / Tan, Lin / Veillon, Lucas / Ajami, Nadim J / Wargo, Jennifer A / Galloway-Peña, Jessica / Shelburne, Samuel / Chemaly, Roy F / Davey, Lauren / Glowacki, Robert W P / Liu, Chen / Rondon, Gabriela / Alousi, Amin M / Molldrem, Jeffrey J / Champlin, Richard E / Shpall, Elizabeth J / Valdivia, Raphael H / Martens, Eric C / Lorenzi, Philip L / Jenq, Robert R

    Cell

    2022  Volume 185, Issue 20, Page(s) 3705–3719.e14

    Abstract: The intestinal microbiota is an important modulator of graft-versus-host disease (GVHD), which often complicates allogeneic hematopoietic stem cell transplantation (allo-HSCT). Broad-spectrum antibiotics such as carbapenems increase the risk for ... ...

    Abstract The intestinal microbiota is an important modulator of graft-versus-host disease (GVHD), which often complicates allogeneic hematopoietic stem cell transplantation (allo-HSCT). Broad-spectrum antibiotics such as carbapenems increase the risk for intestinal GVHD, but mechanisms are not well understood. In this study, we found that treatment with meropenem, a commonly used carbapenem, aggravates colonic GVHD in mice via the expansion of Bacteroides thetaiotaomicron (BT). BT has a broad ability to degrade dietary polysaccharides and host mucin glycans. BT in meropenem-treated allogeneic mice demonstrated upregulated expression of enzymes involved in the degradation of mucin glycans. These mice also had thinning of the colonic mucus layer and decreased levels of xylose in colonic luminal contents. Interestingly, oral xylose supplementation significantly prevented thinning of the colonic mucus layer in meropenem-treated mice. Specific nutritional supplementation strategies, including xylose supplementation, may combat antibiotic-mediated microbiome injury to reduce the risk for intestinal GVHD in allo-HSCT patients.
    MeSH term(s) Animals ; Anti-Bacterial Agents/pharmacology ; Anti-Bacterial Agents/therapeutic use ; Bacteroides ; Carbapenems/pharmacology ; Carbapenems/therapeutic use ; Graft vs Host Disease/drug therapy ; Graft vs Host Disease/etiology ; Hematopoietic Stem Cell Transplantation ; Meropenem ; Mice ; Mucins/metabolism ; Mucus/metabolism ; Polysaccharides/metabolism ; Xylose
    Chemical Substances Anti-Bacterial Agents ; Carbapenems ; Mucins ; Polysaccharides ; Xylose (A1TA934AKO) ; Meropenem (FV9J3JU8B1)
    Language English
    Publishing date 2022-09-29
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 187009-9
    ISSN 1097-4172 ; 0092-8674
    ISSN (online) 1097-4172
    ISSN 0092-8674
    DOI 10.1016/j.cell.2022.09.007
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 1167: Show issues Location:
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  6. Article ; Online: Diet-derived metabolites and mucus link the gut microbiome to fever after cytotoxic cancer treatment.

    Schwabkey, Zaker I / Wiesnoski, Diana H / Chang, Chia-Chi / Tsai, Wen-Bin / Pham, Dung / Ahmed, Saira S / Hayase, Tomo / Ortega Turrubiates, Miriam R / El-Himri, Rawan K / Sanchez, Christopher A / Hayase, Eiko / Frenk Oquendo, Annette C / Miyama, Takahiko / Halsey, Taylor M / Heckel, Brooke E / Brown, Alexandria N / Jin, Yimei / Raybaud, Mathilde / Prasad, Rishika /
    Flores, Ivonne / McDaniel, Lauren / Chapa, Valerie / Lorenzi, Philip L / Warmoes, Marc O / Tan, Lin / Swennes, Alton G / Fowler, Stephanie / Conner, Margaret / McHugh, Kevin / Graf, Tyler / Jensen, Vanessa B / Peterson, Christine B / Do, Kim-Anh / Zhang, Liangliang / Shi, Yushu / Wang, Yinghong / Galloway-Pena, Jessica R / Okhuysen, Pablo C / Daniel-MacDougall, Carrie R / Shono, Yusuke / Burgos da Silva, Marina / Peled, Jonathan U / van den Brink, Marcel R M / Ajami, Nadim / Wargo, Jennifer A / Reddy, Pavan / Valdivia, Raphael H / Davey, Lauren / Rondon, Gabriela / Srour, Samer A / Mehta, Rohtesh S / Alousi, Amin M / Shpall, Elizabeth J / Champlin, Richard E / Shelburne, Samuel A / Molldrem, Jeffrey J / Jamal, Mohamed A / Karmouch, Jennifer L / Jenq, Robert R

    Science translational medicine

    2022  Volume 14, Issue 671, Page(s) eabo3445

    Abstract: Not all patients with cancer and severe neutropenia develop fever, and the fecal microbiome may play a role. In a single-center study of patients undergoing hematopoietic cell transplant ( ...

    Abstract Not all patients with cancer and severe neutropenia develop fever, and the fecal microbiome may play a role. In a single-center study of patients undergoing hematopoietic cell transplant (
    MeSH term(s) Mice ; Animals ; Gastrointestinal Microbiome ; Propionates ; Hematopoietic Stem Cell Transplantation ; Verrucomicrobia ; Mucus/metabolism ; Mucins/metabolism ; Diet ; Neutropenia/metabolism ; Neoplasms/metabolism
    Chemical Substances Propionates ; Mucins
    Language English
    Publishing date 2022-11-16
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2518854-9
    ISSN 1946-6242 ; 1946-6234
    ISSN (online) 1946-6242
    ISSN 1946-6234
    DOI 10.1126/scitranslmed.abo3445
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 6941: Show issues Location:
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