32 results on '"Ramírez-Suástegui, Ciro"'
Search Results
2. Intra-tumoral T cells in pediatric brain tumors display clonal expansion and effector properties
- Author
-
Upadhye, Aditi, Meza Landeros, Kevin E., Ramírez-Suástegui, Ciro, Schmiedel, Benjamin J., Woo, Edwin, Chee, Serena J., Malicki, Denise, Coufal, Nicole G., Gonda, David, Levy, Michael L., Greenbaum, Jason A., Seumois, Grégory, Crawford, John, Roberts, William D., Schoenberger, Stephen P., Cheroutre, Hilde, Ottensmeier, Christian H., Vijayanand, Pandurangan, and Ganesan, Anusha-Preethi
- Published
- 2024
- Full Text
- View/download PDF
3. An integrated cell atlas of the lung in health and disease
- Author
-
Sikkema, Lisa, Ramírez-Suástegui, Ciro, Strobl, Daniel C, Gillett, Tessa E, Zappia, Luke, Madissoon, Elo, Markov, Nikolay S, Zaragosi, Laure-Emmanuelle, Ji, Yuge, Ansari, Meshal, Arguel, Marie-Jeanne, Apperloo, Leonie, Banchero, Martin, Bécavin, Christophe, Berg, Marijn, Chichelnitskiy, Evgeny, Chung, Mei-i, Collin, Antoine, Gay, Aurore CA, Gote-Schniering, Janine, Hooshiar Kashani, Baharak, Inecik, Kemal, Jain, Manu, Kapellos, Theodore S, Kole, Tessa M, Leroy, Sylvie, Mayr, Christoph H, Oliver, Amanda J, von Papen, Michael, Peter, Lance, Taylor, Chase J, Walzthoeni, Thomas, Xu, Chuan, Bui, Linh T, De Donno, Carlo, Dony, Leander, Faiz, Alen, Guo, Minzhe, Gutierrez, Austin J, Heumos, Lukas, Huang, Ni, Ibarra, Ignacio L, Jackson, Nathan D, Kadur Lakshminarasimha Murthy, Preetish, Lotfollahi, Mohammad, Tabib, Tracy, Talavera-López, Carlos, Travaglini, Kyle J, Wilbrey-Clark, Anna, Worlock, Kaylee B, Yoshida, Masahiro, van den Berge, Maarten, Bossé, Yohan, Desai, Tushar J, Eickelberg, Oliver, Kaminski, Naftali, Krasnow, Mark A, Lafyatis, Robert, Nikolic, Marko Z, Powell, Joseph E, Rajagopal, Jayaraj, Rojas, Mauricio, Rozenblatt-Rosen, Orit, Seibold, Max A, Sheppard, Dean, Shepherd, Douglas P, Sin, Don D, Timens, Wim, Tsankov, Alexander M, Whitsett, Jeffrey, Xu, Yan, Banovich, Nicholas E, Barbry, Pascal, Duong, Thu Elizabeth, Falk, Christine S, Meyer, Kerstin B, Kropski, Jonathan A, Pe’er, Dana, Schiller, Herbert B, Tata, Purushothama Rao, Schultze, Joachim L, Teichmann, Sara A, Misharin, Alexander V, Nawijn, Martijn C, Luecken, Malte D, and Theis, Fabian J
- Subjects
Lung ,Genetics ,Underpinning research ,1.1 Normal biological development and functioning ,Generic health relevance ,Respiratory ,Good Health and Well Being ,Humans ,COVID-19 ,Pulmonary Fibrosis ,Lung Neoplasms ,Macrophages ,Lung Biological Network Consortium ,Medical and Health Sciences ,Immunology - Abstract
Single-cell technologies have transformed our understanding of human tissues. Yet, studies typically capture only a limited number of donors and disagree on cell type definitions. Integrating many single-cell datasets can address these limitations of individual studies and capture the variability present in the population. Here we present the integrated Human Lung Cell Atlas (HLCA), combining 49 datasets of the human respiratory system into a single atlas spanning over 2.4 million cells from 486 individuals. The HLCA presents a consensus cell type re-annotation with matching marker genes, including annotations of rare and previously undescribed cell types. Leveraging the number and diversity of individuals in the HLCA, we identify gene modules that are associated with demographic covariates such as age, sex and body mass index, as well as gene modules changing expression along the proximal-to-distal axis of the bronchial tree. Mapping new data to the HLCA enables rapid data annotation and interpretation. Using the HLCA as a reference for the study of disease, we identify shared cell states across multiple lung diseases, including SPP1+ profibrotic monocyte-derived macrophages in COVID-19, pulmonary fibrosis and lung carcinoma. Overall, the HLCA serves as an example for the development and use of large-scale, cross-dataset organ atlases within the Human Cell Atlas.
- Published
- 2023
4. Intermittent PI3Kδ inhibition sustains anti-tumour immunity and curbs irAEs.
- Author
-
Eschweiler, Simon, Ramírez-Suástegui, Ciro, Li, Yingcong, King, Emma, Chudley, Lindsey, Thomas, Jaya, Wood, Oliver, von Witzleben, Adrian, Jeffrey, Danielle, McCann, Katy, Simon, Hayley, Mondal, Monalisa, Wang, Alice, Dicker, Martina, Lopez-Guadamillas, Elena, Chou, Ting-Fang, Dobbs, Nicola, Essame, Louisa, Acton, Gary, Kelly, Fiona, Halbert, Gavin, Sacco, Joseph, Schache, Andrew, Shaw, Richard, McCaul, James, Paterson, Claire, Davies, Joseph, Brennan, Peter, Singh, Rabindra, Loadman, Paul, Wilson, William, Hackshaw, Allan, Seumois, Gregory, Okkenhaug, Klaus, Thomas, Gareth, Jones, Terry, Ay, Ferhat, Friberg, Greg, Vanhaesebroeck, Bart, Vijayanand, Pandurangan, Ottensmeier, Christian, and Kronenberg, Mitchell
- Subjects
Adenosine ,Animals ,Antineoplastic Agents ,Disease Models ,Animal ,Head and Neck Neoplasms ,Humans ,Immunotherapy ,Mice ,Phosphatidylinositol 3-Kinases ,Quinolines ,T-Lymphocytes ,Regulatory - Abstract
Phosphoinositide 3-kinase δ (PI3Kδ) has a key role in lymphocytes, and inhibitors that target this PI3K have been approved for treatment of B cell malignancies1-3. Although studies in mouse models of solid tumours have demonstrated that PI3Kδ inhibitors (PI3Kδi) can induce anti-tumour immunity4,5, its effect on solid tumours in humans remains unclear. Here we assessed the effects of the PI3Kδi AMG319 in human patients with head and neck cancer in a neoadjuvant, double-blind, placebo-controlled randomized phase II trial (EudraCT no. 2014-004388-20). PI3Kδ inhibition decreased the number of tumour-infiltrating regulatory T (Treg) cells and enhanced the cytotoxic potential of tumour-infiltrating T cells. At the tested doses of AMG319, immune-related adverse events (irAEs) required treatment to be discontinued in 12 out of 21 of patients treated with AMG319, suggestive of systemic effects on Treg cells. Accordingly, in mouse models, PI3Kδi decreased the number of Treg cells systemically and caused colitis. Single-cell RNA-sequencing analysis revealed a PI3Kδi-driven loss of tissue-resident colonic ST2 Treg cells, accompanied by expansion of pathogenic T helper 17 (TH17) and type 17 CD8+ T (TC17) cells, which probably contributed to toxicity; this points towards a specific mode of action for the emergence of irAEs. A modified treatment regimen with intermittent dosing of PI3Kδi in mouse models led to a significant decrease in tumour growth without inducing pathogenic T cells in colonic tissue, indicating that alternative dosing regimens might limit toxicity.
- Published
- 2022
5. Cytotoxic CD4+ tissue-resident memory T cells are associated with asthma severity
- Author
-
Herrera-De La Mata, Sara, Ramírez-Suástegui, Ciro, Mistry, Heena, Castañeda-Castro, Francisco Emmanuel, Kyyaly, Mohammad A., Simon, Hayley, Liang, Shu, Lau, Laurie, Barber, Clair, Mondal, Monalisa, Zhang, Hongmei, Arshad, Syed Hasan, Kurukulaaratchy, Ramesh J., Vijayanand, Pandurangan, and Seumois, Grégory
- Published
- 2023
- Full Text
- View/download PDF
6. Human Eosinophils Express a Distinct Gene Expression Program in Response to IL-3 Compared with Common β-Chain Cytokines IL-5 and GM-CSF
- Author
-
Nelson, Ryan K, Brickner, Howard, Panwar, Bharat, Ramírez-Suástegui, Ciro, Herrera-de la Mata, Sara, Liu, Neiman, Diaz, Damaris, Alexander, Laura E Crotty, Ay, Ferhat, Vijayanand, Pandurangan, Seumois, Grégory, and Akuthota, Praveen
- Subjects
Biotechnology ,Genetics ,Lung ,Clinical Research ,Asthma ,2.1 Biological and endogenous factors ,Aetiology ,Cytokines ,Down-Regulation ,Eosinophils ,Gene Expression ,Granulocyte-Macrophage Colony-Stimulating Factor ,Humans ,Interleukin-3 ,Interleukin-5 ,Signal Transduction ,Up-Regulation ,Immunology - Abstract
Despite recent advances in asthma management with anti-IL-5 therapies, many patients have eosinophilic asthma that remains poorly controlled. IL-3 shares a common β subunit receptor with both IL-5 and GM-CSF but, through α-subunit-specific properties, uniquely influences eosinophil biology and may serve as a potential therapeutic target. We aimed to globally characterize the transcriptomic profiles of GM-CSF, IL-3, and IL-5 stimulation on human circulating eosinophils and identify differences in gene expression using advanced statistical modeling. Human eosinophils were isolated from the peripheral blood of healthy volunteers and stimulated with either GM-CSF, IL-3, or IL-5 for 48 h. RNA was then extracted and bulk sequencing performed. DESeq analysis identified differentially expressed genes and weighted gene coexpression network analysis independently defined modules of genes that are highly coexpressed. GM-CSF, IL-3, and IL-5 commonly upregulated 252 genes and downregulated 553 genes, producing a proinflammatory and survival phenotype that was predominantly mediated through TWEAK signaling. IL-3 stimulation yielded the most numbers of differentially expressed genes that were also highly coexpressed (n = 119). These genes were enriched in pathways involving JAK/STAT signaling. GM-CSF and IL-5 stimulation demonstrated redundancy in eosinophil gene expression. In conclusion, IL-3 produces a distinct eosinophil gene expression program among the β-chain receptor cytokines. IL-3-upregulated genes may provide a foundation for research into therapeutics for patients with eosinophilic asthma who do not respond to anti-IL-5 therapies.
- Published
- 2019
7. Intratumoral follicular regulatory T cells curtail anti-PD-1 treatment efficacy
- Author
-
Eschweiler, Simon, Clarke, James, Ramírez-Suástegui, Ciro, Panwar, Bharat, Madrigal, Ariel, Chee, Serena J., Karydis, Ioannis, Woo, Edwin, Alzetani, Aiman, Elsheikh, Somaia, Hanley, C. J., Thomas, G. J., Friedmann, Peter S., Sanchez-Elsner, Tilman, Ay, Ferhat, Ottensmeier, Christian H., and Vijayanand, Pandurangan
- Published
- 2021
- Full Text
- View/download PDF
8. Transcriptomes and metabolism define mouse and human MAIT cell populations
- Author
-
Chandra, Shilpi, primary, Ascui, Gabriel, additional, Riffelmacher, Thomas, additional, Chawla, Ashu, additional, Ramírez-Suástegui, Ciro, additional, Castelan, Viankail C., additional, Seumois, Gregory, additional, Simon, Hayley, additional, Murray, Mallory P., additional, Seo, Goo-Young, additional, Premlal, Ashmitaa L. R., additional, Schmiedel, Benjamin, additional, Verstichel, Greet, additional, Li, Yingcong, additional, Lin, Chia-Hao, additional, Greenbaum, Jason, additional, Lamberti, John, additional, Murthy, Raghav, additional, Nigro, John, additional, Cheroutre, Hilde, additional, Ottensmeier, Christian H., additional, Hedrick, Stephen M., additional, Lu, Li-Fan, additional, Vijayanand, Pandurangan, additional, and Kronenberg, Mitchell, additional
- Published
- 2023
- Full Text
- View/download PDF
9. Sex determination systems in reptiles are related to ambient temperature but not to the level of climatic fluctuation
- Author
-
Cornejo-Páramo, Paola, Lira-Noriega, Andrés, Ramírez-Suástegui, Ciro, Méndez-de-la-Cruz, Fausto R., Székely, Tamás, Urrutia, Araxi O., and Cortez, Diego
- Published
- 2020
- Full Text
- View/download PDF
10. JAML immunotherapy targets recently activated tumor-infiltrating CD8+ T cells
- Author
-
Eschweiler, Simon, primary, Wang, Alice, additional, Ramírez-Suástegui, Ciro, additional, von Witzleben, Adrian, additional, Li, Yingcong, additional, Chee, Serena J., additional, Simon, Hayley, additional, Mondal, Monalisa, additional, Ellis, Matthew, additional, Thomas, Gareth J., additional, Chandra, Vivek, additional, Ottensmeier, Christian H., additional, and Vijayanand, Pandurangan, additional
- Published
- 2023
- Full Text
- View/download PDF
11. Cytotoxic CD4+ tissue-resident memory T cells are associated with asthma severity.
- Author
-
de la Mata, Sara Herrera, primary, Ramírez-Suástegui, Ciro, additional, Mistry, Heena, additional, Kyyaly, Mohammad A., additional, Simon, Hayley, additional, Liang, Shu, additional, Lau, Laurie, additional, Barber, Clair, additional, Mondal, Monalisa, additional, Arshad, Syed Hasan, additional, Kurukulaaratchy, Ramesh J., additional, Vijayanand, Pandurangan, additional, and Seumois, Grégory, additional
- Published
- 2022
- Full Text
- View/download PDF
12. An integrated cell atlas of the human lung in health and disease
- Author
-
Luecken, Malte, primary, Sikkema, Lisa, additional, Strobl, Daniel, additional, Zappia, Luke, additional, Madissoon, Elo, additional, Markov, Nikolay, additional, Zaragosi, Laure-Emmanuelle, additional, Ansari, Meshal, additional, Arguel, Marie-Jeanne, additional, Apperloo, Leonie, additional, Becavin, Christophe, additional, Berg, Marijn, additional, Chichelnitskiy, Evgeny, additional, Chung, Mei-i, additional, Collin, Antoine, additional, Gay, Aurore, additional, Kashani, Baharak Hooshiar, additional, Jain, Manu, additional, Kapellos, Theodore, additional, Kole, Tessa, additional, Mayr, Christoph, additional, von Papen, Michael, additional, Peter, Lance, additional, Ramírez-Suástegui, Ciro, additional, Schniering, Janine, additional, Taylor, Chase, additional, Walzthoeni, Thomas, additional, Xu, Chuan, additional, Bui, Linh, additional, de Donno, Carlo, additional, Dony, Leander, additional, Guo, Minzhe, additional, Gutierrez, Austin, additional, Heumos, Lukas, additional, Huang, Ni, additional, Río, Ignacio Ibarra Del, additional, Jackson, Nathan, additional, Murthy, Preetish Kadur Lakshminarasimha, additional, Lotfollahi, Mohammad, additional, Tabib, Tracy, additional, Talavera-Lopez, Carlos, additional, Travaglini, Kyle, additional, Wilbrey-Clark, Anna, additional, Worlock, Kaylee, additional, Yoshida, Masahiro, additional, Desai, Tushar, additional, Rozenblatt-Rosen, Orit, additional, Falk, Christine, additional, Kaminski, Naftali, additional, Krasnow, Mark, additional, Lafyatis, Robert, additional, Nikolic, Marko, additional, Powell, Joseph, additional, Rajagopal, Jay, additional, Seibold, Max, additional, Sheppard, Dean, additional, Shepherd, Douglas, additional, Teichmann, Sarah, additional, Tsankov, Alexander, additional, Whitsett, Jeffrey, additional, Xu, Yan, additional, Banovich, Nicholas, additional, Barbry, Pascal, additional, Duong, Thu, additional, Meyer, Kerstin, additional, Kropski, Jonathan, additional, Pe'er, Dana, additional, Schiller, Herbert, additional, Tata, Purushothama Rao, additional, Schultze, Joachim, additional, Berge, Maarten van den, additional, Chen, Yuexin, additional, Hagood, James, additional, Hassan, Ahmed, additional, Horvath, Peter, additional, Lundeberg, Joakim, additional, Leroy, Sylvie, additional, Marquette, Charles, additional, Pryhuber, Gloria, additional, Samakovlis, Christos, additional, Sun, Xin, additional, Ware, Lorraine, additional, Zhang, Kun, additional, Misharin, Alexander, additional, Nawijn, Martijn, additional, and Theis, Fabian, additional
- Published
- 2022
- Full Text
- View/download PDF
13. Single-cell eQTL analysis of activated T cell subsets reveals activation and cell type–dependent effects of disease-risk variants
- Author
-
Schmiedel, Benjamin J., primary, Gonzalez-Colin, Cristian, additional, Fajardo, Vicente, additional, Rocha, Job, additional, Madrigal, Ariel, additional, Ramírez-Suástegui, Ciro, additional, Bhattacharyya, Sourya, additional, Simon, Hayley, additional, Greenbaum, Jason A., additional, Peters, Bjoern, additional, Seumois, Grégory, additional, Ay, Ferhat, additional, Chandra, Vivek, additional, and Vijayanand, Pandurangan, additional
- Published
- 2022
- Full Text
- View/download PDF
14. Tumor-infiltrating NK cell subsets associated with the magnitude of T cell response in human lung cancer
- Author
-
awad, Amiera, primary, Ramírez-Suástegui, Ciro, additional, Clarke, James, additional, Panwar, Bharat, additional, Wood, Oliver, additional, Chee, Serena, additional, Thomas, Gareth, additional, Sanchez-Elsner, Tilman, additional, Ottensmeier, Christian, additional, Friedmann, Peter, additional, Vijayanand, Pandurangan, additional, and Ganesan, Anusha-Preethi, additional
- Published
- 2022
- Full Text
- View/download PDF
15. Severely ill COVID-19 patients display impaired exhaustion features in SARS-CoV-2-reactive CD8+ T cells
- Author
-
Kusnadi, Anthony, Ramírez-Suástegui, Ciro, Fajardo, Vicente, Chee, Serena J, Meckiff, Benjamin J, Simon, Hayley, Pelosi, Emanuela, Seumois, Grégory, Ay, Ferhat, Vijayanand, Pandurangan, and Ottensmeier, Christian H
- Subjects
body regions ,Coronavirus ,CD4-Positive T-Lymphocytes ,SARS-CoV-2 ,R-Articles ,fungi ,Immunity ,COVID-19 ,Humans ,macromolecular substances ,CD8-Positive T-Lymphocytes ,skin and connective tissue diseases ,Research Articles - Abstract
Fewer SARS-CoV-2-reactive memory CD8+ T cells with ‘exhaustion’ features are present in COVID-19 patients with severe vs. mild disease., The molecular properties of CD8+ T cells that respond to SARS-CoV-2 infection are not fully known. Here, we report on the single-cell transcriptomes of >80,000 virus-reactive CD8+ T cells, obtained using a modified Antigen-Reactive T cell Enrichment (ARTE) assay, from 39 COVID-19 patients and 10 healthy subjects. COVID-19 patients segregated into two groups based on whether the dominant CD8+ T cell response to SARS-CoV-2 was ‘exhausted’ or not. SARS-CoV-2-reactive cells in the exhausted subset were increased in frequency and displayed lesser cytotoxicity and inflammatory features in COVID-19 patients with mild compared to severe illness. In contrast, SARS-CoV-2-reactive cells in the dominant non-exhausted subset from patients with severe disease showed enrichment of transcripts linked to co-stimulation, pro-survival NF-κB signaling, and anti-apoptotic pathways, suggesting the generation of robust CD8+ T cell memory responses in patients with severe COVID-19 illness. CD8+ T cells reactive to influenza and respiratory syncytial virus from healthy subjects displayed polyfunctional features and enhanced glycolysis. Cells with such features were largely absent in SARS-CoV-2-reactive cells from both COVID-19 patients and healthy controls non-exposed to SARS-CoV-2. Overall, our single-cell analysis revealed substantial diversity in the nature of CD8+ T cells responding to SARS-CoV-2.
- Published
- 2021
16. Severely ill patients with COVID-19 display impaired exhaustion features in SARS-CoV-2–reactive CD8 + T cells
- Author
-
Kusnadi, Anthony, primary, Ramírez-Suástegui, Ciro, additional, Fajardo, Vicente, additional, Chee, Serena J., additional, Meckiff, Benjamin J., additional, Simon, Hayley, additional, Pelosi, Emanuela, additional, Seumois, Grégory, additional, Ay, Ferhat, additional, Vijayanand, Pandurangan, additional, and Ottensmeier, Christian H., additional
- Published
- 2021
- Full Text
- View/download PDF
17. Additional file 1 of Sex determination systems in reptiles are related to ambient temperature but not to the level of climatic fluctuation
- Author
-
Cornejo-Páramo, Paola, Lira-Noriega, Andrés, Ramírez-Suástegui, Ciro, Méndez-De-La-Cruz, Fausto R., Székely, Tamás, Araxi O. Urrutia, and Cortez, Diego
- Abstract
Additional file 1: Figure S1. Phylogenetic relationship between reproductive mode and ambient temperature (N = 213 species). Figure S2. Climate and climatic fluctuations in reptiles with temperature-dependent and genotypic sex determination systems for oviparous species only (n = 182 species), and ambient temperature in relation to the duration of the breeding season for oviparous species only (n = 182 species). Figure S3. World maps showing the distributions and average temperature of species with GSD or TSD and known breeding seasons. Figure S4. Ambient temperature and the variance within the geographic range of the species relative to the size of the geographic range of the species. Figure S5. Seasonality data from reptiles (n = 213) compared to random data. Figure S6. Correlations between continuous life history traits.
- Published
- 2020
- Full Text
- View/download PDF
18. Imbalance of Regulatory and Cytotoxic SARS-CoV-2-Reactive CD4+ T Cells in COVID-19
- Author
-
Meckiff, Benjamin J., primary, Ramírez-Suástegui, Ciro, additional, Fajardo, Vicente, additional, Chee, Serena J., additional, Kusnadi, Anthony, additional, Simon, Hayley, additional, Eschweiler, Simon, additional, Grifoni, Alba, additional, Pelosi, Emanuela, additional, Weiskopf, Daniela, additional, Sette, Alessandro, additional, Ay, Ferhat, additional, Seumois, Grégory, additional, Ottensmeier, Christian H., additional, and Vijayanand, Pandurangan, additional
- Published
- 2020
- Full Text
- View/download PDF
19. Severely ill COVID-19 patients display augmented functional properties in SARS-CoV-2-reactive CD8+T cells
- Author
-
Kusnadi, Anthony, primary, Ramírez-Suástegui, Ciro, additional, Fajardo, Vicente, additional, Chee, Serena J, additional, Meckiff, Benjamin J, additional, Simon, Hayley, additional, Pelosi, Emanuela, additional, Seumois, Grégory, additional, Ay, Ferhat, additional, Vijayanand, Pandurangan, additional, and Ottensmeier, Christian H, additional
- Published
- 2020
- Full Text
- View/download PDF
20. Single-cell transcriptomic analysis of allergen-specific T cells in allergy and asthma
- Author
-
Seumois, Grégory, primary, Ramírez-Suástegui, Ciro, additional, Schmiedel, Benjamin J., additional, Liang, Shu, additional, Peters, Bjoern, additional, Sette, Alessandro, additional, and Vijayanand, Pandurangan, additional
- Published
- 2020
- Full Text
- View/download PDF
21. Single-cell transcriptomic analysis of SARS-CoV-2 reactive CD4+T cells
- Author
-
Meckiff, Benjamin J., primary, Ramírez-Suástegui, Ciro, additional, Fajardo, Vicente, additional, Chee, Serena J, additional, Kusnadi, Anthony, additional, Simon, Hayley, additional, Grifoni, Alba, additional, Pelosi, Emanuela, additional, Weiskopf, Daniela, additional, Sette, Alessandro, additional, Ay, Ferhat, additional, Seumois, Grégory, additional, Ottensmeier, Christian H, additional, and Vijayanand, Pandurangan, additional
- Published
- 2020
- Full Text
- View/download PDF
22. Viviparous Reptile Regarded to Have Temperature-Dependent Sex Determination Has Old XY Chromosomes
- Author
-
Cornejo-Páramo, Paola, primary, Dissanayake, Duminda S B, primary, Lira-Noriega, Andrés, primary, Martínez-Pacheco, Mónica L, primary, Acosta, Armando, primary, Ramírez-Suástegui, Ciro, primary, Méndez-de-la-Cruz, Fausto R, primary, Székely, Tamás, primary, Urrutia, Araxi O, primary, Georges, Arthur, primary, and Cortez, Diego, primary
- Published
- 2020
- Full Text
- View/download PDF
23. Single-Cell Transcriptomic Analysis of SARS-CoV-2 Reactive CD4 + T Cells
- Author
-
Meckiff, Benjamin J., primary, Ramírez-Suástegui, Ciro, additional, Fajardo, Vicente, additional, Chee, Serena J., additional, Kusnadi, Anthony, additional, Simon, Hayley, additional, Grifoni, Alba, additional, Pelosi, Emanuela, additional, Weiskopf, Daniela, additional, Sette, Alessandro, additional, Ay, Ferhat, additional, Seumois, Grégory, additional, Ottensmeier, Christian, additional, and Vijayanand, Pandurangan, additional
- Published
- 2020
- Full Text
- View/download PDF
24. Severely ill patients with COVID-19 display impaired exhaustion features in SARS-CoV-2–reactive CD8+ T cells.
- Author
-
Kusnadi, Anthony, Ramírez-Suástegui, Ciro, Fajardo, Vicente, Chee, Serena J., Meckiff, Benjamin J., Simon, Hayley, Pelosi, Emanuela, Seumois, Grégory, Ay, Ferhat, Vijayanand, Pandurangan, and Ottensmeier, Christian H.
- Abstract
The molecular properties of CD8
+ T cells that respond to SARS-CoV-2 infection are not fully known. Here, we report on the single-cell transcriptomes of >80,000 virus-reactive CD8+ T cells, obtained using a modified antigen-reactive T cell enrichment assay, from 39 patients with COVID-19 and 10 healthy participants. Patients with COVID-19 were segregated into two groups based on whether the dominant CD8+ T cell response to SARS-CoV-2 was "exhausted" or "non-exhausted." SARS-CoV-2–reactive cells in the exhausted subset were increased in frequency and displayed lesser cytotoxicity and inflammatory features in patients with COVID-19 experiencing mild compared with severe illness. In contrast, SARS-CoV-2–reactive cells in the dominant nonexhausted subset from patients with severe disease showed enrichment of transcripts linked to costimulation, prosurvival NF-κB signaling, and antiapoptotic pathways, suggesting the generation of robust CD8+ T cell memory responses in patients with severe COVID-19 illness. CD8+ T cells reactive to influenza and respiratory syncytial virus from healthy participants displayed polyfunctional features and enhanced glycolysis. Cells with such features were largely absent in SARS-CoV-2–reactive cells from both patients with COVID-19 and healthy controls nonexposed to SARS-CoV-2. Overall, our single-cell analysis revealed substantial diversity in the nature of CD8+ T cells responding to SARS-CoV-2. [ABSTRACT FROM AUTHOR]- Published
- 2021
- Full Text
- View/download PDF
25. Male Mutation Bias Is the Main Force Shaping Chromosomal Substitution Rates in Monotreme Mammals
- Author
-
Link, Vivian, primary, Aguilar-Gómez, Diana, additional, Ramírez-Suástegui, Ciro, additional, Hurst, Laurence D., additional, and Cortez, Diego, additional
- Published
- 2017
- Full Text
- View/download PDF
26. Cytotoxic CD4+tissue-resident memory T cells are associated with asthma severity
- Author
-
Herrera-De La Mata, Sara, Ramírez-Suástegui, Ciro, Mistry, Heena, Castañeda-Castro, Francisco Emmanuel, Kyyaly, Mohammad A., Simon, Hayley, Liang, Shu, Lau, Laurie, Barber, Clair, Mondal, Monalisa, Zhang, Hongmei, Arshad, Syed Hasan, Kurukulaaratchy, Ramesh J., Vijayanand, Pandurangan, and Seumois, Grégory
- Abstract
Patients with severe uncontrolled asthma represent a distinct endotype with persistent airway inflammation and remodeling that is refractory to corticosteroid treatment. CD4+TH2 cells play a central role in orchestrating asthma pathogenesis, and biologic therapies targeting their cytokine pathways have had promising outcomes. However, not all patients respond well to such treatment, and their effects are not always durable nor reverse airway remodeling. This observation raises the possibility that other CD4+T cell subsets and their effector molecules may drive airway inflammation and remodeling.
- Published
- 2023
- Full Text
- View/download PDF
27. JAML immunotherapy targets recently activated tumor-infiltrating CD8+T cells
- Author
-
Eschweiler, Simon, Wang, Alice, Ramírez-Suástegui, Ciro, von Witzleben, Adrian, Li, Yingcong, Chee, Serena J., Simon, Hayley, Mondal, Monalisa, Ellis, Matthew, Thomas, Gareth J., Chandra, Vivek, Ottensmeier, Christian H., and Vijayanand, Pandurangan
- Abstract
Junctional adhesion molecule-like protein (JAML) serves as a co-stimulatory molecule in γδ T cells. While it has recently been described as a cancer immunotherapy target in mice, its potential to cause toxicity, specific mode of action with regard to its cellular targets, and whether it can be targeted in humans remain unknown. Here, we show that JAML is induced by T cell receptor engagement, reveal that this induction is linked to cis-regulatory interactions between the CD3Dand JAMLgene loci. When compared with other immunotherapy targets plagued by low target specificity and end-organ toxicity, we find JAML to be mostly restricted to and highly expressed by tissue-resident memory CD8+T cells in multiple cancer types. By delineating the key cellular targets and functional consequences of agonistic anti-JAML therapy in a murine melanoma model, we show its specific mode of action and the reason for its synergistic effects with anti-PD-1.
- Published
- 2023
- Full Text
- View/download PDF
28. JAML immunotherapy targets recently activated tumor-infiltrating CD8 + T cells.
- Author
-
Eschweiler S, Wang A, Ramírez-Suástegui C, von Witzleben A, Li Y, Chee SJ, Simon H, Mondal M, Ellis M, Thomas GJ, Chandra V, Ottensmeier CH, and Vijayanand P
- Subjects
- Humans, Animals, Mice, Junctional Adhesion Molecules, CD8-Positive T-Lymphocytes metabolism, Immunotherapy, Lymphocytes, Tumor-Infiltrating metabolism, Cell Adhesion Molecules metabolism, Neoplasms
- Abstract
Junctional adhesion molecule-like protein (JAML) serves as a co-stimulatory molecule in γδ T cells. While it has recently been described as a cancer immunotherapy target in mice, its potential to cause toxicity, specific mode of action with regard to its cellular targets, and whether it can be targeted in humans remain unknown. Here, we show that JAML is induced by T cell receptor engagement, reveal that this induction is linked to cis-regulatory interactions between the CD3D and JAML gene loci. When compared with other immunotherapy targets plagued by low target specificity and end-organ toxicity, we find JAML to be mostly restricted to and highly expressed by tissue-resident memory CD8
+ T cells in multiple cancer types. By delineating the key cellular targets and functional consequences of agonistic anti-JAML therapy in a murine melanoma model, we show its specific mode of action and the reason for its synergistic effects with anti-PD-1., Competing Interests: Declaration of interests The La Jolla Institute of Immunology has filed a patent “Methods for modulating an immune response to cancer or tumor cells” related to this work, and S.E., P.V., and C.H.O. are co-inventors on this patent., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)- Published
- 2023
- Full Text
- View/download PDF
29. Severely ill COVID-19 patients display impaired exhaustion features in SARS-CoV-2-reactive CD8 + T cells.
- Author
-
Kusnadi A, Ramírez-Suástegui C, Fajardo V, Chee SJ, Meckiff BJ, Simon H, Pelosi E, Seumois G, Ay F, Vijayanand P, and Ottensmeier CH
- Subjects
- Adult, Aged, Aged, 80 and over, Female, Glycolysis immunology, Humans, Immunologic Memory immunology, Male, Middle Aged, NF-kappa B immunology, Signal Transduction immunology, Single-Cell Analysis methods, Young Adult, CD8-Positive T-Lymphocytes immunology, COVID-19 immunology, SARS-CoV-2 immunology
- Abstract
The molecular properties of CD8
+ T cells that respond to SARS-CoV-2 infection are not fully known. Here, we report on the single-cell transcriptomes of >80,000 virus-reactive CD8+ T cells, obtained using a modified Antigen-Reactive T cell Enrichment (ARTE) assay, from 39 COVID-19 patients and 10 healthy subjects. COVID-19 patients segregated into two groups based on whether the dominant CD8+ T cell response to SARS-CoV-2 was 'exhausted' or not. SARS-CoV-2-reactive cells in the exhausted subset were increased in frequency and displayed lesser cytotoxicity and inflammatory features in COVID-19 patients with mild compared to severe illness. In contrast, SARS-CoV-2-reactive cells in the dominant non-exhausted subset from patients with severe disease showed enrichment of transcripts linked to co-stimulation, pro-survival NF-κB signaling, and anti-apoptotic pathways, suggesting the generation of robust CD8+ T cell memory responses in patients with severe COVID-19 illness. CD8+ T cells reactive to influenza and respiratory syncytial virus from healthy subjects displayed polyfunctional features and enhanced glycolysis. Cells with such features were largely absent in SARS-CoV-2-reactive cells from both COVID-19 patients and healthy controls non-exposed to SARS-CoV-2. Overall, our single-cell analysis revealed substantial diversity in the nature of CD8+ T cells responding to SARS-CoV-2., (Copyright © 2021, American Association for the Advancement of Science.)- Published
- 2021
- Full Text
- View/download PDF
30. Imbalance of Regulatory and Cytotoxic SARS-CoV-2-Reactive CD4 + T Cells in COVID-19.
- Author
-
Meckiff BJ, Ramírez-Suástegui C, Fajardo V, Chee SJ, Kusnadi A, Simon H, Eschweiler S, Grifoni A, Pelosi E, Weiskopf D, Sette A, Ay F, Seumois G, Ottensmeier CH, and Vijayanand P
- Subjects
- Adult, Aged, Aged, 80 and over, Antibodies, Viral blood, Antibodies, Viral immunology, CD4 Lymphocyte Count, COVID-19 epidemiology, COVID-19 virology, Cohort Studies, England epidemiology, Female, Humans, Male, Middle Aged, Reverse Transcriptase Polymerase Chain Reaction, Severity of Illness Index, Single-Cell Analysis methods, Spike Glycoprotein, Coronavirus immunology, COVID-19 immunology, SARS-CoV-2 genetics, T Follicular Helper Cells immunology, T-Lymphocytes, Cytotoxic immunology, T-Lymphocytes, Regulatory immunology, Transcriptome
- Abstract
The contribution of CD4
+ T cells to protective or pathogenic immune responses to SARS-CoV-2 infection remains unknown. Here, we present single-cell transcriptomic analysis of >100,000 viral antigen-reactive CD4+ T cells from 40 COVID-19 patients. In hospitalized patients compared to non-hospitalized patients, we found increased proportions of cytotoxic follicular helper cells and cytotoxic T helper (TH ) cells (CD4-CTLs) responding to SARS-CoV-2 and reduced proportion of SARS-CoV-2-reactive regulatory T cells (TREG ). Importantly, in hospitalized COVID-19 patients, a strong cytotoxic TFH response was observed early in the illness, which correlated negatively with antibody levels to SARS-CoV-2 spike protein. Polyfunctional TH 1 and TH 17 cell subsets were underrepresented in the repertoire of SARS-CoV-2-reactive CD4+ T cells compared to influenza-reactive CD4+ T cells. Together, our analyses provide insights into the gene expression patterns of SARS-CoV-2-reactive CD4+ T cells in distinct disease severities., Competing Interests: Declaration of Interests The authors declare no competing interests., (Crown Copyright © 2020. Published by Elsevier Inc. All rights reserved.)- Published
- 2020
- Full Text
- View/download PDF
31. Severely ill COVID-19 patients display augmented functional properties in SARS-CoV-2-reactive CD8 + T cells.
- Author
-
Kusnadi A, Ramírez-Suástegui C, Fajardo V, Chee SJ, Meckiff BJ, Simon H, Pelosi E, Seumois G, Ay F, Vijayanand P, and Ottensmeier CH
- Abstract
The molecular properties of CD8
+ T cells that respond to SARS-CoV-2 infection are not fully known. Here, we report on the single-cell transcriptomes of >80,000 virus-reactive CD8+ T cells from 39 COVID-19 patients and 10 healthy subjects. COVID-19 patients segregated into two groups based on whether the dominant CD8+ T cell response to SARS-CoV-2 was 'exhausted' or not. SARS-CoV-2-reactive cells in the exhausted subset were increased in frequency and displayed lesser cytotoxicity and inflammatory features in COVID-19 patients with mild compared to severe illness. In contrast, SARS-CoV-2-reactive cells in the non-exhausted subsets from patients with severe disease showed enrichment of transcripts linked to co-stimulation, pro-survival NF-κB signaling, and anti-apoptotic pathways, suggesting the generation of robust CD8+ T cell memory responses in patients with severe COVID-19 illness. CD8+ T cells reactive to influenza and respiratory syncytial virus from healthy subjects displayed polyfunctional features. Cells with such features were mostly absent in SARS-CoV-2 responsive cells from both COVID-19 patients and healthy controls non-exposed to SARS-CoV-2. Overall, our single-cell analysis revealed substantial diversity in the nature of CD8+ T cells responding to SARS-CoV-2.- Published
- 2020
- Full Text
- View/download PDF
32. Single-cell transcriptomic analysis of SARS-CoV-2 reactive CD4 + T cells.
- Author
-
Meckiff BJ, Ramírez-Suástegui C, Fajardo V, Chee SJ, Kusnadi A, Simon H, Grifoni A, Pelosi E, Weiskopf D, Sette A, Ay F, Seumois G, Ottensmeier CH, and Vijayanand P
- Abstract
The contribution of CD4
+ T cells to protective or pathogenic immune responses to SARS-CoV-2 infection remains unknown. Here, we present large-scale single-cell transcriptomic analysis of viral antigen-reactive CD4+ T cells from 32 COVID-19 patients. In patients with severe disease compared to mild disease, we found increased proportions of cytotoxic follicular helper (TFH ) cells and cytotoxic T helper cells (CD4-CTLs) responding to SARS-CoV-2, and reduced proportion of SARS-CoV-2 reactive regulatory T cells. Importantly, the CD4-CTLs were highly enriched for the expression of transcripts encoding chemokines that are involved in the recruitment of myeloid cells and dendritic cells to the sites of viral infection. Polyfunctional T helper (TH )1 cells and TH 17 cell subsets were underrepresented in the repertoire of SARS-CoV-2-reactive CD4+ T cells compared to influenza-reactive CD4+ T cells. Together, our analyses provide so far unprecedented insights into the gene expression patterns of SARS-CoV-2 reactive CD4+ T cells in distinct disease severities.- Published
- 2020
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.