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Article: Disrupting CD38-driven T cell dysfunction restores sensitivity to cancer immunotherapy.

Revach, Or-Yam / Cicerchia, Angelina M / Shorer, Ofir / Petrova, Boryana / Anderson, Seth / Park, Joshua / Chen, Lee / Mehta, Arnav / Wright, Samuel J / McNamee, Niamh / Tal-Mason, Aya / Cattaneo, Giulia / Tiwari, Payal / Xie, Hongyan / Sweere, Johanna M / Cheng, Li-Chun / Sigal, Natalia / Enrico, Elizabeth / Miljkovic, Marisa /

Evans, Shane A / Nguyen, Ngan / Whidden, Mark E / Srinivasan, Ramji / Spitzer, Matthew H / Sun, Yi / Sharova, Tatyana / Lawless, Aleigha R / Michaud, William A / Rasmussen, Martin Q / Fang, Jacy / Palin, Claire A / Chen, Feng / Wang, Xinhui / Ferrone, Cristina R / Lawrence, Donald P / Sullivan, Ryan J / Liu, David / Sachdeva, Uma M / Sen, Debattama R / Flaherty, Keith T / Manguso, Robert T / Bod, Lloyd / Kellis, Manolis / Boland, Genevieve M / Yizhak, Keren / Yang, Jiekun / Kanarek, Naama / Sade-Feldman, Moshe / Hacohen, Nir / Jenkins, Russell W

bioRxiv : the preprint server for biology

2024

Abstract: A central problem in cancer immunotherapy with immune checkpoint blockade (ICB) is the development of resistance, which affects 50% of patients with metastatic ... ...

Abstract	A central problem in cancer immunotherapy with immune checkpoint blockade (ICB) is the development of resistance, which affects 50% of patients with metastatic melanoma
Language	English
Publishing date	2024-03-26
Publishing country	United States
Document type	Preprint
DOI	10.1101/2024.02.12.579184
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Article ; Online: Decoding T cell state-specific regulomes in cancer.

Escobar, Giulia / Anderson, Ana C

Cell research

2024

Language	English
Publishing date	2024-01-19
Publishing country	England
Document type	Journal Article
ZDB-ID	1319303-x
ISSN	1748-7838 ; 1001-0602
ISSN (online)	1748-7838
ISSN	1001-0602
DOI	10.1038/s41422-024-00926-3
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Article ; Online: T Cells from NOD-

Racine, Jeremy J / Chapman, Harold D / Doty, Rosalinda / Cairns, Brynn M / Hines, Timothy J / Tadenev, Abigail L D / Anderson, Laura C / Green, Torrian / Dyer, Meaghan E / Wotton, Janine M / Bichler, Zoë / White, Jacqueline K / Ettinger, Rachel / Burgess, Robert W / Serreze, David V

Journal of immunology (Baltimore, Md. : 1950)

2020 Volume 205, Issue 8, Page(s) 2026–2038

Abstract: It has become increasingly appreciated that autoimmune responses against neuronal components play an important role in type 1 diabetes (T1D) pathogenesis. In fact, a large proportion of islet-infiltrating B lymphocytes in the NOD mouse model of T1D ... ...

Abstract	It has become increasingly appreciated that autoimmune responses against neuronal components play an important role in type 1 diabetes (T1D) pathogenesis. In fact, a large proportion of islet-infiltrating B lymphocytes in the NOD mouse model of T1D produce Abs directed against the neuronal type III intermediate filament protein peripherin. NOD-
MeSH term(s)	Animals ; CD4-Positive T-Lymphocytes/pathology ; CD8-Positive T-Lymphocytes/immunology ; CD8-Positive T-Lymphocytes/pathology ; Diabetes Mellitus, Experimental/genetics ; Diabetes Mellitus, Experimental/immunology ; Diabetes Mellitus, Experimental/pathology ; Diabetes Mellitus, Type 1/genetics ; Diabetes Mellitus, Type 1/immunology ; Mice ; Mice, Inbred NOD ; Mice, SCID ; Mice, Transgenic ; Nerve Tissue/immunology ; Nerve Tissue/pathology ; Neuritis, Autoimmune, Experimental/genetics ; Neuritis, Autoimmune, Experimental/immunology ; Neuritis, Autoimmune, Experimental/pathology ; Pancreas/immunology ; Pancreas/pathology
Keywords	covid19
Language	English
Publishing date	2020-09-16
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	3056-9
ISSN	1550-6606 ; 0022-1767 ; 1048-3233 ; 1047-7381
ISSN (online)	1550-6606
ISSN	0022-1767 ; 1048-3233 ; 1047-7381
DOI	10.4049/jimmunol.2000114
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Zs.MG 28: Show issues

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Article ; Online: Increased vesicular dynamics and nanoscale clustering of IL-2 after T cell activation.

Saed, Badeia / Ramseier, Neal T / Perera, Thilini / Anderson, Jesse / Burnett, Jacob / Gunasekara, Hirushi / Burgess, Alyssa / Jing, Haoran / Hu, Ying S

Biophysical journal

2024

Abstract: T cells coordinate intercellular communication through the meticulous regulation of cytokine ... valuable insights into the temporal and spatial mechanisms involved in regulation. Employing Jurkat E6-1 T ... particle tracking and the nanoscale distribution of intracellular IL-2 in fixed T cells using ...

Abstract	T cells coordinate intercellular communication through the meticulous regulation of cytokine secretion. Direct visualization of vesicular transport and intracellular distribution of cytokines provides valuable insights into the temporal and spatial mechanisms involved in regulation. Employing Jurkat E6-1 T cells and interleukin-2 (IL-2) as a model system, we investigated vesicular dynamics using single-particle tracking and the nanoscale distribution of intracellular IL-2 in fixed T cells using superresolution microscopy. Live-cell imaging revealed that in vitro activation resulted in increased vesicular dynamics. Direct stochastic optical reconstruction microscopy and 3D structured illumination microscopy revealed nanoscale clustering of IL-2. In vitro activation correlated with spatial accumulation of IL-2 nanoclusters into more pronounced and elongated clusters. These observations provide visual evidence that accelerated vesicular transport and spatial concatenation of IL-2 clusters at the nanoscale may constitute a potential mechanism for modulating cytokine release by Jurkat T cells.
Language	English
Publishing date	2024-03-26
Publishing country	United States
Document type	Journal Article
ZDB-ID	218078-9
ISSN	1542-0086 ; 0006-3495
ISSN (online)	1542-0086
ISSN	0006-3495
DOI	10.1016/j.bpj.2024.03.029
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Zs.A 235: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 2: Show issues

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Article ; Online: Transcriptional signatures associated with persisting CD19 CAR-T cells in children with leukemia.

Nature medicine

2023 Volume 29, Issue 7, Page(s) 1700–1709

Abstract: ... ALL), CD19-targeting chimeric antigen receptor (CAR)-T cells often induce durable remissions, which requires ... the persistence of CAR-T cells. In this study, we systematically analyzed CD19 CAR-T cells of 10 children with R/R ... B-ALL enrolled in the CARPALL trial via high-throughput single-cell gene expression and T cell ...

Abstract	In the context of relapsed and refractory childhood pre-B cell acute lymphoblastic leukemia (R/R B-ALL), CD19-targeting chimeric antigen receptor (CAR)-T cells often induce durable remissions, which requires the persistence of CAR-T cells. In this study, we systematically analyzed CD19 CAR-T cells of 10 children with R/R B-ALL enrolled in the CARPALL trial via high-throughput single-cell gene expression and T cell receptor sequencing of infusion products and serial blood and bone marrow samples up to 5 years after infusion. We show that long-lived CAR-T cells developed a CD4/CD8 double-negative phenotype with an exhausted-like memory state and distinct transcriptional signature. This persistence signature was dominant among circulating CAR-T cells in all children with a long-lived treatment response for which sequencing data were sufficient (4/4, 100%). The signature was also present across T cell subsets and clonotypes, indicating that persisting CAR-T cells converge transcriptionally. This persistence signature was also detected in two adult patients with chronic lymphocytic leukemia with decade-long remissions who received a different CD19 CAR-T cell product. Examination of single T cell transcriptomes from a wide range of healthy and diseased tissues across children and adults indicated that the persistence signature may be specific to long-lived CAR-T cells. These findings raise the possibility that a universal transcriptional signature of clinically effective, persistent CD19 CAR-T cells exists.
MeSH term(s)	Humans ; Antigens, CD19/genetics ; Immunotherapy, Adoptive ; Leukemia, Lymphocytic, Chronic, B-Cell ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy ; Receptors, Antigen, T-Cell ; Remission Induction ; T-Lymphocytes
Chemical Substances	Antigens, CD19 ; Receptors, Antigen, T-Cell ; CD19 molecule, human
Language	English
Publishing date	2023-07-06
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1220066-9
ISSN	1546-170X ; 1078-8956
ISSN (online)	1546-170X
ISSN	1078-8956
DOI	10.1038/s41591-023-02415-3
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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)
Zs.MG 39: Show issues

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Article ; Online: Enhancing Efficacy of TCR-engineered CD4 + T Cells Via Coexpression of CD8α.

Anderson, Victoria E / Brilha, Sara S / Weber, Anika M / Pachnio, Annette / Wiedermann, Guy E / Dauleh, Sumaya / Ahmed, Tina / Pope, George R / Quinn, Laura L / Docta, Roslin Y / Quattrini, Adriano / Masters, Siobhan / Cartwright, Neil / Viswanathan, Preetha / Melchiori, Luca / Rice, Louise V / Sevko, Alexandra / Gueguen, Claire / Saini, Manoj /

Tavano, Barbara / Abbott, Rachel J M / Silk, Jonathan D / Laugel, Bruno / Sanderson, Joseph P / Gerry, Andrew B

Journal of immunotherapy (Hagerstown, Md. : 1997)

2023 Volume 46, Issue 4, Page(s) 132–144

Abstract: Adoptive cell therapy with T cells expressing affinity-enhanced T-cell receptors (TCRs) is ... a promising treatment for solid tumors. Efforts are ongoing to further engineer these T cells to increase ... In the present study, we investigated one such approach: T cells were transduced with a lentiviral vector ...

Abstract	Adoptive cell therapy with T cells expressing affinity-enhanced T-cell receptors (TCRs) is a promising treatment for solid tumors. Efforts are ongoing to further engineer these T cells to increase the depth and durability of clinical responses and broaden efficacy toward additional indications. In the present study, we investigated one such approach: T cells were transduced with a lentiviral vector to coexpress an affinity-enhanced HLA class I-restricted TCR directed against MAGE-A4 alongside a CD8α coreceptor. We hypothesized that this approach would enhance CD4 + T-cell helper and effector functions, possibly leading to a more potent antitumor response. Activation of transduced CD4 + T cells was measured by detecting CD40 ligand expression on the surface and cytokine and chemokine secretion from CD4 + T cells and dendritic cells cultured with melanoma-associated antigen A4 + tumor cells. In addition, T-cell cytotoxic activity against 3-dimensional tumor spheroids was measured. Our data demonstrated that CD4 + T cells coexpressing the TCR and CD8α coreceptor displayed enhanced responses, including CD40 ligand expression, interferon-gamma secretion, and cytotoxic activity, along with improved dendritic cell activation. Therefore, our study supports the addition of the CD8α coreceptor to HLA class I-restricted TCR-engineered T cells to enhance CD4 + T-cell functions, which may potentially improve the depth and durability of antitumor responses in patients.
MeSH term(s)	Humans ; CD40 Ligand ; CD4-Positive T-Lymphocytes ; T-Lymphocytes, Helper-Inducer ; Receptors, Antigen, T-Cell/metabolism ; Antineoplastic Agents
Chemical Substances	CD40 Ligand (147205-72-9) ; Receptors, Antigen, T-Cell ; Antineoplastic Agents
Language	English
Publishing date	2023-02-27
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1064067-8
ISSN	1537-4513 ; 1053-8550 ; 1524-9557
ISSN (online)	1537-4513
ISSN	1053-8550 ; 1524-9557
DOI	10.1097/CJI.0000000000000456
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Article ; Online: A three-stage developmental pathway for human Vγ9Vδ2 T cells within the postnatal thymus.

Perriman, Louis / Tavakolinia, Naeimeh / Jalali, Sedigheh / Li, Shuo / Hickey, Peter F / Amann-Zalcenstein, Daniela / Ho, William Wing Ho / Baldwin, Tracey M / Piers, Adam T / Konstantinov, Igor E / Anderson, Jeremy / Stanley, Edouard G / Licciardi, Paul V / Kannourakis, George / Naik, Shalin H / Koay, Hui-Fern / Mackay, Laura K / Berzins, Stuart P / Pellicci, Daniel G

Science immunology

2023 Volume 8, Issue 85, Page(s) eabo4365

Abstract: Vγ9Vδ2 T cells are the largest population of γδ T cells in adults and can play important roles ... Vγ9Vδ2 T cells are derived from the fetal liver and thymus and that the postnatal thymus plays little ... functional assays, and precursor-product experiments to define the development pathway of Vγ9Vδ2 T ...

Abstract	Vγ9Vδ2 T cells are the largest population of γδ T cells in adults and can play important roles in providing effective immunity against cancer and infection. Many studies have suggested that peripheral Vγ9Vδ2 T cells are derived from the fetal liver and thymus and that the postnatal thymus plays little role in the development of these cells. More recent evidence suggested that these cells may also develop postnatally in the thymus. Here, we used high-dimensional flow cytometry, transcriptomic analysis, functional assays, and precursor-product experiments to define the development pathway of Vγ9Vδ2 T cells in the postnatal thymus. We identify three distinct stages of development for Vγ9Vδ2 T cells in the postnatal thymus that are defined by the progressive acquisition of functional potential and major changes in the expression of transcription factors, chemokines, and other surface markers. Furthermore, our analysis of donor-matched thymus and blood revealed that the molecular requirements for the development of functional Vγ9Vδ2 T cells are delivered predominantly by the postnatal thymus and not in the periphery. Tbet and Eomes, which are required for IFN-γ and TNFα expression, are up-regulated as Vγ9Vδ2 T cells mature in the thymus, and mature thymic Vγ9Vδ2 T cells rapidly express high levels of these cytokines after stimulation. Similarly, the postnatal thymus programs Vγ9Vδ2 T cells to express the cytolytic molecules, perforin, granzyme A, and granzyme K. This study provides a greater understanding of how Vγ9Vδ2 T cells develop in humans and may lead to opportunities to manipulate these cells to treat human diseases.
MeSH term(s)	Adult ; Humans ; T-Lymphocyte Subsets ; Receptors, Antigen, T-Cell, gamma-delta ; Thymus Gland ; Gene Expression Profiling
Chemical Substances	Receptors, Antigen, T-Cell, gamma-delta
Language	English
Publishing date	2023-07-14
Publishing country	United States
Document type	Journal Article
ISSN	2470-9468
ISSN (online)	2470-9468
DOI	10.1126/sciimmunol.abo4365
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Article ; Online: mRNA vaccine against malaria tailored for liver-resident memory T cells.

Ganley, Mitch / Holz, Lauren E / Minnell, Jordan J / de Menezes, Maria N / Burn, Olivia K / Poa, Kean Chan Yew / Draper, Sarah L / English, Kieran / Chan, Susanna T S / Anderson, Regan J / Compton, Benjamin J / Marshall, Andrew J / Cozijnsen, Anton / Chua, Yu Cheng / Ge, Zhengyu / Farrand, Kathryn J / Mamum, John C / Xu, Calvin / Cockburn, Ian A /

Yui, Katsuyuki / Bertolino, Patrick / Gras, Stephanie / Le Nours, Jérôme / Rossjohn, Jamie / Fernandez-Ruiz, Daniel / McFadden, Geoffrey I / Ackerley, David F / Painter, Gavin F / Hermans, Ian F / Heath, William R

Nature immunology

2023 Volume 24, Issue 9, Page(s) 1487–1498

Abstract: ... resident memory T cells (Trm cells) have recently been shown to control liver-stage infections, we embarked ... sporozoites in mice, addition of an agonist that recruits T cell help from type I natural killer T cells under ...

Abstract	Malaria is caused by Plasmodium species transmitted by Anopheles mosquitoes. Following a mosquito bite, Plasmodium sporozoites migrate from skin to liver, where extensive replication occurs, emerging later as merozoites that can infect red blood cells and cause symptoms of disease. As liver tissue-resident memory T cells (Trm cells) have recently been shown to control liver-stage infections, we embarked on a messenger RNA (mRNA)-based vaccine strategy to induce liver Trm cells to prevent malaria. Although a standard mRNA vaccine was unable to generate liver Trm or protect against challenge with Plasmodium berghei sporozoites in mice, addition of an agonist that recruits T cell help from type I natural killer T cells under mRNA-vaccination conditions resulted in significant generation of liver Trm cells and effective protection. Moreover, whereas previous exposure of mice to blood-stage infection impaired traditional vaccines based on attenuated sporozoites, mRNA vaccination was unaffected, underlining the potential for such a rational mRNA-based strategy in malaria-endemic regions.
MeSH term(s)	Animals ; Mice ; Memory T Cells ; Malaria/prevention & control ; Liver ; Malaria Vaccines ; Plasmodium berghei/genetics ; CD8-Positive T-Lymphocytes
Chemical Substances	Malaria Vaccines
Language	English
Publishing date	2023-07-20
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2016987-5
ISSN	1529-2916 ; 1529-2908
ISSN (online)	1529-2916
ISSN	1529-2908
DOI	10.1038/s41590-023-01562-6
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Zs.A 5294: 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)
Zs.MG 42: Show issues

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Article ; Online: Short-Term Dietary Restriction Potentiates an Anti-Inflammatory Circulating Mucosal-Associated Invariant T-Cell Response.

Fazzone, Brian / Anderson, Erik M / Rozowsky, Jared M / Yu, Xuanxuan / O'Malley, Kerri A / Robinson, Scott / Scali, Salvatore T / Cai, Guoshuai / Berceli, Scott A

Nutrients

2024 Volume 16, Issue 8

Abstract: ... associated invariant T-cells (MAITs) are enriched on mucosal surfaces and in circulation, bridge innate and ... TNFα), and T-cell co-stimulation (CD40/CD40L, CD28), whereas genes associated with anti-inflammatory ...

Abstract	Short-term protein-calorie dietary restriction (StDR) is a promising preoperative strategy for modulating postoperative inflammation. We have previously shown marked gut microbial activity during StDR, but relationships between StDR, the gut microbiome, and systemic immunity remain poorly understood. Mucosal-associated invariant T-cells (MAITs) are enriched on mucosal surfaces and in circulation, bridge innate and adaptive immunity, are sensitive to gut microbial changes, and may mediate systemic responses to StDR. Herein, we characterized the MAIT transcriptomic response to StDR using single-cell RNA sequencing of human PBMCs and evaluated gut microbial species-level changes through sequencing of stool samples. Healthy volunteers underwent 4 days of DR during which blood and stool samples were collected before, during, and after DR. MAITs composed 2.4% of PBMCs. More MAIT genes were differentially downregulated during DR, particularly genes associated with MAIT activation (CD69), regulation of pro-inflammatory signaling (IL1, IL6, IL10, TNFα), and T-cell co-stimulation (CD40/CD40L, CD28), whereas genes associated with anti-inflammatory IL10 signaling were upregulated. Stool analysis showed a decreased abundance of multiple MAIT-stimulating
MeSH term(s)	Humans ; Mucosal-Associated Invariant T Cells/immunology ; Gastrointestinal Microbiome ; Male ; Adult ; Caloric Restriction ; Female ; Feces/microbiology ; Inflammation/immunology ; Young Adult ; Healthy Volunteers ; Transcriptome
Language	English
Publishing date	2024-04-22
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2518386-2
ISSN	2072-6643 ; 2072-6643
ISSN (online)	2072-6643
ISSN	2072-6643
DOI	10.3390/nu16081245
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Article ; Online: It Didn’t Go Away

Simone Rambotti / Caroline Wolski / Kathryn Freeman Anderson

COVID, Vol 3, Iss 27, Pp 370-

The Political and Social Determinants of COVID-19 Mortality Rates across Counties in the United States

2023 Volume 380

Abstract: Research over the last several years has demonstrated a wide variety of inequalities in the COVID-19 pandemic by socio-demographic characteristics, place, and political and religious ideology. In this study, by combining several county-level data sources, ...

Abstract	Research over the last several years has demonstrated a wide variety of inequalities in the COVID-19 pandemic by socio-demographic characteristics, place, and political and religious ideology. In this study, by combining several county-level data sources, we examine how the social conditions of counties across the United States relate to their differential COVID-19 mortality rates. We find that percent Black, percent Hispanic, and income inequality are all positively related to higher mortality rates at the county level. Moreover, the percentage of the population that voted for Trump in the 2020 election was a significant and substantively large predictor of higher mortality rates. We also include healthcare-related variables, but compared to the social circumstances of the pandemic, these effects are relatively small. These results indicate that the social conditions of areas are strong predictors of how counties have experienced the pandemic and where the greatest loss of life has occurred.
Keywords	COVID-19 ; mortality ; political polarization ; social determinants of health ; Specialties of internal medicine ; RC581-951
Language	English
Publishing date	2023-03-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
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