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Article: Functional impairment of "helpless" CD8

van der Heide, Verena / Davenport, Bennett / Cubitt, Beatrice / Roudko, Vladimir / Choo, Daniel / Humblin, Etienne / Jhun, Kevin / Angeliadis, Krista / Dawson, Travis / Furtado, Glaucia / Kamphorst, Alice / Ahmed, Rafi / de la Torre, Juan Carlos / Homann, Dirk

bioRxiv : the preprint server for biology

2024

Abstract: Generation of functional ... ...

Abstract	Generation of functional CD8
Language	English
Publishing date	2024-01-26
Publishing country	United States
Document type	Preprint
DOI	10.1101/2024.01.22.576725
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Article ; Online: Modelling Free-Living and Particle-Associated Bacterial Assemblages across the Deep and Hypoxic Lower St. Lawrence Estuary.

Cui, Ting Ting / Dawson, Travis J / McLatchie, Susan / Dunn, Katherine / Bielawski, Joseph / Walsh, David A

mSphere

2020 Volume 5, Issue 3

Abstract: The Estuary and Gulf of St. Lawrence (EGSL) in eastern Canada are among the largest and most productive coastal ecosystems in the world. Very little information on bacterial diversity exists, hampering our understanding of the relationships between ... ...

Abstract	The Estuary and Gulf of St. Lawrence (EGSL) in eastern Canada are among the largest and most productive coastal ecosystems in the world. Very little information on bacterial diversity exists, hampering our understanding of the relationships between bacterial community structure and biogeochemical function in the EGSL. During the productive spring period, we investigated free-living and particle-associated bacterial communities across the stratified waters of the Lower St. Lawrence Estuary, including the particle-rich surface and bottom boundary layers. Modelling of community structure based on 16S rRNA gene and transcript diversity identified bacterial assemblages specifically associated with four habitat types defined by water mass (upper water or lower water column) and size fraction (free living or particle associated). Assemblages from the upper waters represent sets of cooccurring bacterial populations that are widely distributed across Lower St. Lawrence Estuary surface waters and likely key contributors to organic matter degradation during the spring. In addition, we provide strong evidence that particles in deep hypoxic waters and the bottom boundary layer support a metabolically active bacterial community that is compositionally distinct from those of surface particles and the free-living communities. Among the distinctive features of the bacterial assemblage associated with lower-water particles was the presence of uncultivated lineages of
MeSH term(s)	Anaerobiosis ; Bacteria/classification ; Bacterial Physiological Phenomena ; Canada ; Estuaries ; Genetic Variation ; Microbiota ; Seasons ; Seawater/microbiology
Language	English
Publishing date	2020-05-20
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2379-5042
ISSN (online)	2379-5042
DOI	10.1128/mSphere.00364-20
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Article ; Online: Immunophenotypic correlates of sustained MRD negativity in patients with multiple myeloma.

Nature communications

2023 Volume 14, Issue 1, Page(s) 5335

Abstract: The role of the immune microenvironment in maintaining disease remission in patients with multiple myeloma (MM) is not well understood. In this study, we comprehensively profile the immune system in patients with newly diagnosed MM receiving continuous ... ...

Abstract	The role of the immune microenvironment in maintaining disease remission in patients with multiple myeloma (MM) is not well understood. In this study, we comprehensively profile the immune system in patients with newly diagnosed MM receiving continuous lenalidomide maintenance therapy with the aim of discovering correlates of long-term treatment response. Leveraging single-cell RNA sequencing and T cell receptor β sequencing of the peripheral blood and CyTOF mass cytometry of the bone marrow, we longitudinally characterize the immune landscape in 23 patients before and one year after lenalidomide exposure. We compare patients achieving sustained minimal residual disease (MRD) negativity to patients who never achieved or were unable to maintain MRD negativity. We observe that the composition of the immune microenvironment in both the blood and the marrow varied substantially according to both MRD negative status and history of autologous stem cell transplant, supporting the hypothesis that the immune microenvironment influences the depth and duration of treatment response.
MeSH term(s)	Humans ; Multiple Myeloma/drug therapy ; Lenalidomide ; Immunophenotyping ; Patients ; Receptors, Antigen, T-Cell, alpha-beta ; Tumor Microenvironment
Chemical Substances	Lenalidomide (F0P408N6V4) ; Receptors, Antigen, T-Cell, alpha-beta
Language	English
Publishing date	2023-09-02
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-023-40966-8
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Article ; Online: TREM2 macrophages drive NK cell paucity and dysfunction in lung cancer.

Park, Matthew D / Reyes-Torres, Ivan / LeBerichel, Jessica / Hamon, Pauline / LaMarche, Nelson M / Hegde, Samarth / Belabed, Meriem / Troncoso, Leanna / Grout, John A / Magen, Assaf / Humblin, Etienne / Nair, Achuth / Molgora, Martina / Hou, Jinchao / Newman, Jenna H / Farkas, Adam M / Leader, Andrew M / Dawson, Travis / D'Souza, Darwin /

Hamel, Steven / Sanchez-Paulete, Alfonso Rodriguez / Maier, Barbara / Bhardwaj, Nina / Martin, Jerome C / Kamphorst, Alice O / Kenigsberg, Ephraim / Casanova-Acebes, Maria / Horowitz, Amir / Brown, Brian D / De Andrade, Lucas Ferrari / Colonna, Marco / Marron, Thomas U / Merad, Miriam

Nature immunology

2023 Volume 24, Issue 5, Page(s) 792–801

Abstract: Natural killer (NK) cells are commonly reduced in human tumors, enabling many to evade surveillance. Here, we sought to identify cues that alter NK cell activity in tumors. We found that, in human lung cancer, the presence of NK cells inversely ... ...

Abstract	Natural killer (NK) cells are commonly reduced in human tumors, enabling many to evade surveillance. Here, we sought to identify cues that alter NK cell activity in tumors. We found that, in human lung cancer, the presence of NK cells inversely correlated with that of monocyte-derived macrophages (mo-macs). In a murine model of lung adenocarcinoma, we show that engulfment of tumor debris by mo-macs triggers a pro-tumorigenic program governed by triggering receptor expressed on myeloid cells 2 (TREM2). Genetic deletion of Trem2 rescued NK cell accumulation and enabled an NK cell-mediated regression of lung tumors. TREM2
MeSH term(s)	Humans ; Mice ; Animals ; Killer Cells, Natural ; Macrophages ; Lung Neoplasms ; Myeloid Cells ; Membrane Glycoproteins/genetics ; Receptors, Immunologic/genetics
Chemical Substances	TREM2 protein, human ; Membrane Glycoproteins ; Receptors, Immunologic ; Trem2 protein, mouse
Language	English
Publishing date	2023-04-20
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2016987-5
ISSN	1529-2916 ; 1529-2908
ISSN (online)	1529-2916
ISSN	1529-2908
DOI	10.1038/s41590-023-01475-4
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Article ; Online: Gut-associated lymphoid tissue attrition associates with response to anti-α4β7 therapy in ulcerative colitis.

Canales-Herrerias, Pablo / Uzzan, Mathieu / Seki, Akihiro / Czepielewski, Rafael S / Verstockt, Bram / Livanos, Alexandra E / Raso, Fiona / Dunn, Alexandra / Dai, Daniel / Wang, Andrew / Al-Taie, Zainab / Martin, Jerome / Laurent, Thomas / Ko, Huaibin M / Tokuyama, Minami / Tankelevich, Michael / Meringer, Hadar / Cossarini, Francesca / Jha, Divya /

Krek, Azra / Paulsen, John D / Taylor, Matthew D / Nakadar, Mohammad Zuber / Wong, Joshua / Erlich, Emma C / Mintz, Rachel L / Onufer, Emily J / Helmink, Beth A / Sharma, Keshav / Rosenstein, Adam / Ganjian, Danielle / Chung, Grace / Dawson, Travis / Juarez, Julius / Yajnik, Vijay / Cerutti, Andrea / Faith, Jeremiah J / Suarez-Farinas, Mayte / Argmann, Carmen / Petralia, Francesca / Randolph, Gwendalyn J / Polydorides, Alexandros D / Reboldi, Andrea / Colombel, Jean-Frederic / Mehandru, Saurabh

Science immunology

2024 Volume 9, Issue 94, Page(s) eadg7549

Abstract: Vedolizumab (VDZ) is a first-line treatment in ulcerative colitis (UC) that targets the α4β7- mucosal vascular addressin cell adhesion molecule 1 (MAdCAM-1) axis. To determine the mechanisms of action of VDZ, we examined five distinct cohorts of patients ...

Abstract	Vedolizumab (VDZ) is a first-line treatment in ulcerative colitis (UC) that targets the α4β7- mucosal vascular addressin cell adhesion molecule 1 (MAdCAM-1) axis. To determine the mechanisms of action of VDZ, we examined five distinct cohorts of patients with UC. A decrease in naïve B and T cells in the intestines and gut-homing (β7
MeSH term(s)	Humans ; Animals ; Mice ; Colitis, Ulcerative/drug therapy ; Integrins ; Intestinal Mucosa ; Peyer's Patches ; Immunoglobulin G/therapeutic use
Chemical Substances	Integrins ; Immunoglobulin G
Language	English
Publishing date	2024-04-19
Publishing country	United States
Document type	Journal Article
ISSN	2470-9468
ISSN (online)	2470-9468
DOI	10.1126/sciimmunol.adg7549
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Article: Shift of lung macrophage composition is associated with COVID-19 disease severity and recovery.

Chen, Steven T / Park, Matthew D / Del Valle, Diane Marie / Buckup, Mark / Tabachnikova, Alexandra / Simons, Nicole W / Mouskas, Konstantinos / Lee, Brian / Geanon, Daniel / D'Souza, Darwin / Dawson, Travis / Marvin, Robert / Nie, Kai / Thompson, Ryan C / Zhao, Zhen / LeBerichel, Jessica / Chang, Christie / Jamal, Hajra / Chaddha, Udit /

Mathews, Kusum / Acquah, Samuel / Brown, Stacey-Ann / Reiss, Michelle / Harkin, Timothy / Feldmann, Marc / Powell, Charles A / Hook, Jaime L / Kim-Schulze, Seunghee / Rahman, Adeeb H / Brown, Brian D / Beckmann, Noam D / Gnjatic, Sacha / Kenigsberg, Ephraim / Charney, Alexander W / Merad, Miriam

bioRxiv : the preprint server for biology

2022

Abstract: Though it has been 2 years since the start of the Coronavirus Disease 19 (COVID-19) pandemic, COVID-19 continues to be a worldwide health crisis. Despite the development of preventive vaccines, very little progress has been made to identify curative ... ...

Abstract	Though it has been 2 years since the start of the Coronavirus Disease 19 (COVID-19) pandemic, COVID-19 continues to be a worldwide health crisis. Despite the development of preventive vaccines, very little progress has been made to identify curative therapies to treat COVID-19 and other inflammatory diseases which remain a major unmet need in medicine. Our study sought to identify drivers of disease severity and death to develop tailored immunotherapy strategies to halt disease progression. Here we assembled the Mount Sinai COVID-19 Biobank which was comprised of ~600 hospitalized patients followed longitudinally during the peak of the pandemic. Moderate disease and survival were associated with a stronger antigen (Ag) presentation and effector T cell signature, while severe disease and death were associated with an altered Ag presentation signature, increased numbers of circulating inflammatory, immature myeloid cells, and extrafollicular activated B cells associated with autoantibody formation. Strikingly, we found that in severe COVID-19 patients, lung tissue resident alveolar macrophages (AM) were not only severely depleted, but also had an altered Ag presentation signature, and were replaced by inflammatory monocytes and monocyte-derived macrophages (MoMΦ). Notably, the size of the AM pool correlated with recovery or death, while AM loss and functionality were restored in patients that recovered. These data therefore suggest that local and systemic myeloid cell dysregulation is a driver of COVID-19 severity and that modulation of AM numbers and functionality in the lung may be a viable therapeutic strategy for the treatment of critical lung inflammatory illnesses.
Language	English
Publishing date	2022-01-12
Publishing country	United States
Document type	Preprint
DOI	10.1101/2022.01.11.475918
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Article ; Online: Limited extent and consequences of pancreatic SARS-CoV-2 infection.

van der Heide, Verena / Jangra, Sonia / Cohen, Phillip / Rathnasinghe, Raveen / Aslam, Sadaf / Aydillo, Teresa / Geanon, Daniel / Handler, Diana / Kelley, Geoffrey / Lee, Brian / Rahman, Adeeb / Dawson, Travis / Qi, Jingjing / D'Souza, Darwin / Kim-Schulze, Seunghee / Panzer, Julia K / Caicedo, Alejandro / Kusmartseva, Irina / Posgai, Amanda L /

Atkinson, Mark A / Albrecht, Randy A / García-Sastre, Adolfo / Rosenberg, Brad R / Schotsaert, Michael / Homann, Dirk

Cell reports

2022 Volume 38, Issue 11, Page(s) 110508

Abstract: Concerns that infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent of coronavirus disease 2019 (COVID-19), may cause new-onset diabetes persist in an evolving research landscape, and precise risk assessment ... ...

Abstract	Concerns that infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent of coronavirus disease 2019 (COVID-19), may cause new-onset diabetes persist in an evolving research landscape, and precise risk assessment is hampered by, at times, conflicting evidence. Here, leveraging comprehensive single-cell analyses of in vitro SARS-CoV-2-infected human pancreatic islets, we demonstrate that productive infection is strictly dependent on the SARS-CoV-2 entry receptor ACE2 and targets practically all pancreatic cell types. Importantly, the infection remains highly circumscribed and largely non-cytopathic and, despite a high viral burden in infected subsets, promotes only modest cellular perturbations and inflammatory responses. Similar experimental outcomes are also observed after islet infection with endemic coronaviruses. Thus, the limits of pancreatic SARS-CoV-2 infection, even under in vitro conditions of enhanced virus exposure, challenge the proposition that in vivo targeting of β cells by SARS-CoV-2 precipitates new-onset diabetes. Whether restricted pancreatic damage and immunological alterations accrued by COVID-19 increase cumulative diabetes risk, however, remains to be evaluated.
MeSH term(s)	COVID-19 ; Diabetes Mellitus ; Humans ; Insulin-Secreting Cells ; Pancreas ; SARS-CoV-2
Language	English
Publishing date	2022-02-21
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2649101-1
ISSN	2211-1247 ; 2211-1247
ISSN (online)	2211-1247
ISSN	2211-1247
DOI	10.1016/j.celrep.2022.110508
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Article ; Online: Intratumoral dendritic cell-CD4

Magen, Assaf / Hamon, Pauline / Fiaschi, Nathalie / Soong, Brian Y / Park, Matthew D / Mattiuz, Raphaël / Humblin, Etienne / Troncoso, Leanna / D'souza, Darwin / Dawson, Travis / Kim, Joel / Hamel, Steven / Buckup, Mark / Chang, Christie / Tabachnikova, Alexandra / Schwartz, Hara / Malissen, Nausicaa / Lavin, Yonit / Soares-Schanoski, Alessandra /

Giotti, Bruno / Hegde, Samarth / Ioannou, Giorgio / Gonzalez-Kozlova, Edgar / Hennequin, Clotilde / Le Berichel, Jessica / Zhao, Zhen / Ward, Stephen C / Fiel, Isabel / Kou, Baijun / Dobosz, Michael / Li, Lianjie / Adler, Christina / Ni, Min / Wei, Yi / Wang, Wei / Atwal, Gurinder S / Kundu, Kunal / Cygan, Kamil J / Tsankov, Alexander M / Rahman, Adeeb / Price, Colles / Fernandez, Nicolas / He, Jiang / Gupta, Namita T / Kim-Schulze, Seunghee / Gnjatic, Sacha / Kenigsberg, Ephraim / Deering, Raquel P / Schwartz, Myron / Marron, Thomas U / Thurston, Gavin / Kamphorst, Alice O / Merad, Miriam

Nature medicine

2023 Volume 29, Issue 6, Page(s) 1389–1399

Abstract: Despite no apparent defects in T cell priming and recruitment to tumors, a large subset of T cell rich tumors fail to respond to immune checkpoint blockade (ICB). We leveraged a neoadjuvant anti-PD-1 trial in patients with hepatocellular carcinoma (HCC), ...

Abstract	Despite no apparent defects in T cell priming and recruitment to tumors, a large subset of T cell rich tumors fail to respond to immune checkpoint blockade (ICB). We leveraged a neoadjuvant anti-PD-1 trial in patients with hepatocellular carcinoma (HCC), as well as additional samples collected from patients treated off-label, to explore correlates of response to ICB within T cell-rich tumors. We show that ICB response correlated with the clonal expansion of intratumoral CXCL13
MeSH term(s)	Humans ; Carcinoma, Hepatocellular/drug therapy ; CD8-Positive T-Lymphocytes ; Liver Neoplasms/pathology ; Programmed Cell Death 1 Receptor ; T-Lymphocytes, Helper-Inducer ; Cell Differentiation ; Dendritic Cells/pathology
Chemical Substances	Programmed Cell Death 1 Receptor
Language	English
Publishing date	2023-06-15
Publishing country	United States
Document type	Journal Article
ZDB-ID	1220066-9
ISSN	1546-170X ; 1078-8956
ISSN (online)	1546-170X
ISSN	1078-8956
DOI	10.1038/s41591-023-02345-0
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Zs.A 4212: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article: Gut-associated lymphoid tissue attrition associates with response to anti-α4β7 therapy in ulcerative colitis.

Canales-Herrerias, Pablo / Uzzan, Mathieu / Seki, Akihiro / Czepielewski, Rafael S / Verstockt, Bram / Livanos, Alexandra / Raso, Fiona / Dunn, Alexandra / Dai, Daniel / Wang, Andrew / Al-Taie, Zainab / Martin, Jerome / Ko, Huaibin M / Tokuyama, Minami / Tankelevich, Michael / Meringer, Hadar / Cossarini, Francesca / Jha, Divya / Krek, Azra /

bioRxiv : the preprint server for biology

2023

Abstract: Targeting the α4β7-MAdCAM-1 axis with vedolizumab (VDZ) is a front-line therapeutic paradigm in ulcerative colitis (UC). However, mechanism(s) of action (MOA) of VDZ remain relatively undefined. Here, we examined three distinct cohorts of patients with ... ...

Abstract	Targeting the α4β7-MAdCAM-1 axis with vedolizumab (VDZ) is a front-line therapeutic paradigm in ulcerative colitis (UC). However, mechanism(s) of action (MOA) of VDZ remain relatively undefined. Here, we examined three distinct cohorts of patients with UC (n=83, n=60, and n=21), to determine the effect of VDZ on the mucosal and peripheral immune system. Transcriptomic studies with protein level validation were used to study drug MOA using conventional and transgenic murine models. We found a significant decrease in colonic and ileal naïve B and T cells and circulating gut-homing plasmablasts (β7
Language	English
Publishing date	2023-01-20
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.01.19.524731
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Article ; Online: Comprehensive Characterization of the Multiple Myeloma Immune Microenvironment Using Integrated scRNA-seq, CyTOF, and CITE-seq Analysis.

Yao, Lijun / Jayasinghe, Reyka G / Lee, Brian H / Bhasin, Swati S / Pilcher, William / Doxie, Deon Bryant / Gonzalez-Kozlova, Edgar / Dasari, Surendra / Fiala, Mark A / Pita-Juarez, Yered / Strausbauch, Michael / Kelly, Geoffrey / Thomas, Beena E / Kumar, Shaji K / Cho, Hearn Jay / Anderson, Emilie / Wendl, Michael C / Dawson, Travis / D'souza, Darwin /

Oh, Stephen T / Cheloni, Giulia / Li, Ying / DiPersio, John F / Rahman, Adeeb H / Dhodapkar, Kavita M / Kim-Schulze, Seunghee / Vij, Ravi / Vlachos, Ioannis S / Mehr, Shaadi / Hamilton, Mark / Auclair, Daniel / Kourelis, Taxiarchis / Avigan, David / Dhodapkar, Madhav V / Gnjatic, Sacha / Bhasin, Manoj K / Ding, Li

Cancer research communications

2022 Volume 2, Issue 10, Page(s) 1255–1265

Abstract: As part of the Multiple Myeloma Research Foundation (MMRF) immune atlas pilot project, we compared immune cells of multiple myeloma bone marrow samples from 18 patients assessed by single-cell RNA sequencing (scRNA-seq), mass cytometry (CyTOF), and ... ...

Abstract	As part of the Multiple Myeloma Research Foundation (MMRF) immune atlas pilot project, we compared immune cells of multiple myeloma bone marrow samples from 18 patients assessed by single-cell RNA sequencing (scRNA-seq), mass cytometry (CyTOF), and cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq) to understand the concordance of measurements among single-cell techniques. Cell type abundances are relatively consistent across the three approaches, while variations are observed in T cells, macrophages, and monocytes. Concordance and correlation analysis of cell type marker gene expression across different modalities highlighted the importance of choosing cell type marker genes best suited to particular modalities. By integrating data from these three assays, we found International Staging System stage 3 patients exhibited decreased CD4 Significance: scRNA-seq, CyTOF, and CITE-seq are increasingly used for evaluating cellular heterogeneity. Understanding their concordances is of great interest. To date, this study is the most comprehensive examination of the measurement of the immune microenvironment in multiple myeloma using the three techniques. Moreover, we identified markers predicted to be significantly associated with multiple myeloma rapid progression.
MeSH term(s)	Humans ; Transcriptome/genetics ; CD8-Positive T-Lymphocytes ; Multiple Myeloma/genetics ; Pilot Projects ; Single-Cell Gene Expression Analysis ; Tumor Microenvironment/genetics
Language	English
Publishing date	2022-10-25
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2767-9764
ISSN (online)	2767-9764
DOI	10.1158/2767-9764.CRC-22-0022
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