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Article ; Online: Response to Comment on "An Injectable Hydrogel to Modulate T Cells for Cancer Immunotherapy".

Zhang, Di / Luan, Yuxia

Small (Weinheim an der Bergstrasse, Germany)

2024 , Page(s) e2307724

Language	English
Publishing date	2024-05-16
Publishing country	Germany
Document type	Journal Article
ZDB-ID	2168935-0
ISSN	1613-6829 ; 1613-6810
ISSN (online)	1613-6829
ISSN	1613-6810
DOI	10.1002/smll.202307724
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Article ; Online: Targeting the epigenome to reinvigorate T cells for cancer immunotherapy.

Xiong, Dian / Zhang, Lu / Sun, Zhi-Jun

Military Medical Research

2023 Volume 10, Issue 1, Page(s) 59

Abstract: Cancer immunotherapy using immune-checkpoint inhibitors (ICIs) has revolutionized the field ... of cancer treatment; however, ICI efficacy is constrained by progressive dysfunction of CD8 ...

Abstract	Cancer immunotherapy using immune-checkpoint inhibitors (ICIs) has revolutionized the field of cancer treatment; however, ICI efficacy is constrained by progressive dysfunction of CD8
MeSH term(s)	Humans ; T-Lymphocytes ; Epigenome ; Lymphocytes, Tumor-Infiltrating ; Immunotherapy ; Neoplasms/genetics ; Neoplasms/therapy
Language	English
Publishing date	2023-12-04
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2768940-2
ISSN	2054-9369 ; 2054-9369
ISSN (online)	2054-9369
ISSN	2054-9369
DOI	10.1186/s40779-023-00496-2
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Article ; Online: Mechano-modulation of T cells for cancer immunotherapy.

Hyun, Jeongeun / Kim, So Jung / Cho, Sung-Dae / Kim, Hae-Won

Biomaterials

2023 Volume 297, Page(s) 122101

Abstract: ... activation of immune cells (mainly T cells) for effective caner immunotherapy. Immune cells are highly sensitive ... Immunotherapy, despite its promise for future anti-cancer approach, faces significant challenges ... for effective cancer immunotherapy, and discuss future prospects and challenges in this field. ...

Abstract	Immunotherapy, despite its promise for future anti-cancer approach, faces significant challenges, such as off-tumor side effects, innate or acquired resistance, and limited infiltration of immune cells into stiffened extracellular matrix (ECM). Recent studies have highlighted the importance of mechano-modulation/-activation of immune cells (mainly T cells) for effective caner immunotherapy. Immune cells are highly sensitive to the applied physical forces and matrix mechanics, and reciprocally shape the tumor microenvironment. Engineering T cells with tuned properties of materials (e.g., chemistry, topography, and stiffness) can improve their expansion and activation ex vivo, and their ability to mechano-sensing the tumor specific ECM in vivo where they perform cytotoxic effects. T cells can also be exploited to secrete enzymes that soften ECM, thus increasing tumor infiltration and cellular therapies. Furthermore, T cells, such as chimeric antigen receptor (CAR)-T cells, genomic engineered to be spatiotemporally controllable by physical stimuli (e.g., ultrasound, heat, or light), can mitigate adverse off-tumor effects. In this review, we communicate these recent cutting-edge endeavors devoted to mechano-modulating/-activating T cells for effective cancer immunotherapy, and discuss future prospects and challenges in this field.
MeSH term(s)	Humans ; T-Lymphocytes ; Immunotherapy ; Neoplasms/therapy ; Cell- and Tissue-Based Therapy ; Immunotherapy, Adoptive ; Tumor Microenvironment
Language	English
Publishing date	2023-04-01
Publishing country	Netherlands
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	603079-8
ISSN	1878-5905 ; 0142-9612
ISSN (online)	1878-5905
ISSN	0142-9612
DOI	10.1016/j.biomaterials.2023.122101
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Article ; Online: Dynamics and specificities of T cells in cancer immunotherapy.

Oliveira, Giacomo / Wu, Catherine J

Nature reviews. Cancer

2023 Volume 23, Issue 5, Page(s) 295–316

Abstract: ... immunotherapy. We highlight those T cell subsets associated with productive T cell responses and discuss how ... Recent advances in cancer immunotherapy - ranging from immune-checkpoint blockade therapy ... diverse immunotherapies might leverage the pre-existing tumour-reactive T cell pool or instruct de novo ...

Abstract	Recent advances in cancer immunotherapy - ranging from immune-checkpoint blockade therapy to adoptive cellular therapy and vaccines - have revolutionized cancer treatment paradigms, yet the variability in clinical responses to these agents has motivated intense interest in understanding how the T cell landscape evolves with respect to response to immune intervention. Over the past decade, the advent of multidimensional single-cell technologies has provided the unprecedented ability to dissect the constellation of cell states of lymphocytes within a tumour microenvironment. In particular, the rapidly expanding capacity to definitively link intratumoural phenotypes with the antigen specificity of T cells provided by T cell receptors (TCRs) has now made it possible to focus on investigating the properties of T cells with tumour-specific reactivity. Moreover, the assessment of TCR clonality has enabled a molecular approach to track the trajectories, clonal dynamics and phenotypic changes of antitumour T cells over the course of immunotherapeutic intervention. Here, we review the current knowledge on the cellular states and antigen specificities of antitumour T cells and examine how fine characterization of T cell dynamics in patients has provided meaningful insights into the mechanisms underlying effective cancer immunotherapy. We highlight those T cell subsets associated with productive T cell responses and discuss how diverse immunotherapies might leverage the pre-existing tumour-reactive T cell pool or instruct de novo generation of antitumour specificities. Future studies aimed at elucidating the factors associated with the elicitation of productive antitumour T cell immunity are anticipated to instruct the design of more efficacious treatment strategies.
MeSH term(s)	Humans ; T-Lymphocytes ; Neoplasms ; Immunotherapy/methods ; Immunity ; Treatment Outcome ; Immunotherapy, Adoptive ; Tumor Microenvironment
Language	English
Publishing date	2023-04-12
Publishing country	England
Document type	Journal Article ; Review ; Research Support, N.I.H., Extramural
ZDB-ID	2062767-1
ISSN	1474-1768 ; 1474-175X
ISSN (online)	1474-1768
ISSN	1474-175X
DOI	10.1038/s41568-023-00560-y
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Zs.A 5563: 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 ; Online: The emerging roles of γδ T cells in cancer immunotherapy.

Mensurado, Sofia / Blanco-Domínguez, Rafael / Silva-Santos, Bruno

Nature reviews. Clinical oncology

2023 Volume 20, Issue 3, Page(s) 178–191

Abstract: ... and promising approach for cancer immunotherapy. The unique features of γδ T cells, including ... Current cancer immunotherapies are primarily predicated on αβ T cells, with a stringent dependence ... clinical studies involving very small numbers of patients, γδ T cells are now being explored as a viable ...

Abstract	Current cancer immunotherapies are primarily predicated on αβ T cells, with a stringent dependence on MHC-mediated presentation of tumour-enriched peptides or unique neoantigens that can limit their efficacy and applicability in various contexts. After two decades of preclinical research and preliminary clinical studies involving very small numbers of patients, γδ T cells are now being explored as a viable and promising approach for cancer immunotherapy. The unique features of γδ T cells, including their tissue tropisms, antitumour activity that is independent of neoantigen burden and conventional MHC-dependent antigen presentation, and combination of typical properties of T cells and natural killer cells, make them very appealing effectors in multiple cancer settings. Herein, we review the main functions of γδ T cells in antitumour immunity, focusing on human γδ T cell subsets, with a particular emphasis on the differences between Vδ1
MeSH term(s)	Humans ; Receptors, Antigen, T-Cell, gamma-delta ; T-Lymphocytes ; Neoplasms/therapy ; Immunotherapy ; Antigen Presentation ; T-Lymphocyte Subsets
Chemical Substances	Receptors, Antigen, T-Cell, gamma-delta
Language	English
Publishing date	2023-01-09
Publishing country	England
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	2491410-1
ISSN	1759-4782 ; 1759-4774
ISSN (online)	1759-4782
ISSN	1759-4774
DOI	10.1038/s41571-022-00722-1
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Zs.A 6029: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG)
Zs.MG 103: Show issues

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Article: [Development of "Off the Shelf" T Cells for Cancer Immunotherapy].

Nagano, Seiji / Kawamoto, Hiroshi

Gan to kagaku ryoho. Cancer & chemotherapy

2023 Volume 50, Issue 5, Page(s) 561–566

Abstract: In the area of cancer immunotherapy, the efficacy of strategies in which patient derived T cells ... been developing a method to generate T cells from iPS cells transduced with a certain T cell receptor ... However, some issues have remained to be addressed; the method using autologous T cells is costly and time consuming ...

Abstract	In the area of cancer immunotherapy, the efficacy of strategies in which patient derived T cells are genetically modified ex vivo and administered to patients has been demonstrated. However, some issues have remained to be addressed; the method using autologous T cells is costly and time consuming, and their quality is unstable. The time consuming problem can be solved by preparing allogeneic T cells in advance. Peripheral blood is being considered as a source of allogeneic T cells, and methods are being explored to avoid the risk of rejection or GVHD, but even so the issues of cost and quality stability still remain. On the other hand, use of pluripotent stem cells such as iPS cells or ES cells as material of T cells may solve the cost issue and achieve homogeneity of products. The authors group has been developing a method to generate T cells from iPS cells transduced with a certain T cell receptor gene, and is currently preparing for clinical trials. We believe that, when this strategy is realized, it becomes possible to deliver a universal and homogeneous T cell preparation immediately when needed.
MeSH term(s)	Humans ; T-Lymphocytes ; Immunotherapy ; Induced Pluripotent Stem Cells ; Genes, T-Cell Receptor ; Neoplasms/therapy ; Immunotherapy, Adoptive
Language	Japanese
Publishing date	2023-05-23
Publishing country	Japan
Document type	English Abstract ; Journal Article
ZDB-ID	604842-0
ISSN	0385-0684
ISSN	0385-0684
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Article ; Online: Targeting the activin receptor 1C on CD4+ T cells for cancer immunotherapy.

Zheng, Ying / Lebid, Andriana / Chung, Liam / Fu, Juan / Wang, Xiaoxu / Otrocol, Andrea / Zarif, Jelani C / Yu, Hong / Llosa, Nicolas J / Pardoll, Drew M

Oncoimmunology

2024 Volume 13, Issue 1, Page(s) 2297503

Abstract: ... a potential candidate for cancer immunotherapy. ... induced regulatory T cells (Tregs), particularly when TGF-beta was limited in the culture medium. Database ... our in vitro studies suggest that activins promote differentiation of naïve CD4+ cells into Foxp3-expressing ...

Abstract	Activins, members of the TGF-beta superfamily, have been isolated and identified in the endocrine system, but have not been substantially investigated in the context of the immune system and endocrine-unrelated cancers. Here, we demonstrated that tumor-bearing mice had elevated systemic activin levels, which correlated directly with tumor burden. Likewise, cancer patients have elevated plasma activin levels compared to healthy controls. We observed that both tumor and immune cells could be sources of activins. Importantly, our in vitro studies suggest that activins promote differentiation of naïve CD4+ cells into Foxp3-expressing induced regulatory T cells (Tregs), particularly when TGF-beta was limited in the culture medium. Database and qRT-PCR analysis of sorted major immune cell subsets in mice revealed that activin receptor 1c (ActRIC) was uniquely expressed on Tregs and that both ActRIC and ActRIIB (activin receptor 2b) were highly upregulated during iTreg differentiation. ActRIC-deficient naïve CD4+ cells were found to be defective in iTreg generation both in vitro and in vivo. Treg suppression assays were also performed, and ActRIC deficiency did not change the function or stability of iTregs. Mice lacking ActRIC or mice treated with monoclonal anti-ActRIC antibody were more resistant to tumor progression than wild-type controls. This phenotype was correlated with reduced expression of Foxp3 in CD4+ cells in the tumor microenvironment. In light of the information presented above, blocking activin-ActRIC signaling is a promising and disease-specific strategy to impede the accumulation of immunosuppressive iTregs in cancer. Therefore, it is a potential candidate for cancer immunotherapy.
MeSH term(s)	Humans ; Mice ; Animals ; CD4-Positive T-Lymphocytes ; Activin Receptors/metabolism ; Transforming Growth Factor beta/metabolism ; Immunotherapy ; Neoplasms/therapy ; Forkhead Transcription Factors/genetics ; Forkhead Transcription Factors/metabolism ; Activins/metabolism ; Tumor Microenvironment
Chemical Substances	Activin Receptors (EC 2.7.11.30) ; Transforming Growth Factor beta ; Forkhead Transcription Factors ; Activins (104625-48-1)
Language	English
Publishing date	2024-01-08
Publishing country	United States
Document type	Journal Article
ZDB-ID	2645309-5
ISSN	2162-402X ; 2162-402X
ISSN (online)	2162-402X
ISSN	2162-402X
DOI	10.1080/2162402X.2023.2297503
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Article ; Online: Releasing the restraints of Vγ9Vδ2 T-cells in cancer immunotherapy.

Ridgley, Laura A / Caron, Jonathan / Dalgleish, Angus / Bodman-Smith, Mark

Frontiers in immunology

2023 Volume 13, Page(s) 1065495

Abstract: ... inhibitory receptors on Vγ9Vδ2 T-cells to assess potential avenues of regulation to target with immunotherapy ... T-cells in immunotherapy. ... a mechanism with the potential to be utilised by tumour cells to subvert Vγ9Vδ2 T-cell cytotoxicity. This work ...

Abstract	Objectives: Vγ9Vδ2 T-cells are a subset of T-cells with a crucial role in immunosurveillance which can be activated and expanded by multiple means to stimulate effector responses. Little is known about the expression of checkpoint molecules on this cell population and whether the ligation of these molecules can regulate their activity. The aim of this study was to assess the expression of both activatory and inhibitory receptors on Vγ9Vδ2 T-cells to assess potential avenues of regulation to target with immunotherapy. Methods: Expression of various activatory and inhibitory receptors was assessed on Vγ9Vδ2 T-cells by flow cytometry following activation and expansion using zoledronic acid (ZA) and Bacillus Calmette-Guérin (BCG). Expression of these markers and production of effector molecules was also examined following co-culture with various tumour cell targets. The effect of immune checkpoint blockade on Vγ9Vδ2 T-cells was also explored. Results: Vγ9Vδ2 T-cells expressed high levels of activatory markers both at baseline and following stimulation. Vγ9Vδ2 T-cells expressed variable levels of inhibitory checkpoint receptors with many being upregulated following stimulation. Expression of these markers is further modulated upon co-culture with tumour cells with changes reflecting activation and effector functions. Despite their high expression of inhibitory receptors when cultured with tumour cells expressing cognate ligands there was no effect on Vδ2+ T-cell cytotoxic capacity or cytokine production with immune checkpoint blockade. Conclusions: Our work suggests the expression of checkpoint receptors present on Vγ9Vδ2 T-cells which may provide a mechanism with the potential to be utilised by tumour cells to subvert Vγ9Vδ2 T-cell cytotoxicity. This work suggests important candidates for blockade by ICI therapy in order to increase the successful use of Vγ9Vδ2 T-cells in immunotherapy.
MeSH term(s)	Humans ; T-Lymphocytes ; Immune Checkpoint Inhibitors/metabolism ; Receptors, Antigen, T-Cell, gamma-delta/metabolism ; Lymphocyte Activation ; Immunotherapy ; Neoplasms/therapy ; Neoplasms/metabolism
Chemical Substances	Immune Checkpoint Inhibitors ; Receptors, Antigen, T-Cell, gamma-delta
Language	English
Publishing date	2023-01-13
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2022.1065495
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Article ; Online: CRISPR-Cas gene knockouts to optimize engineered T cells for cancer immunotherapy.

De Castro, Valentine / Galaine, Jeanne / Loyon, Romain / Godet, Yann

Cancer gene therapy

2024

Abstract: ... T cells. These factors are intricately linked to the success of adoptive cell therapy. Recently, CRISPR ... These technologies have allowed the discovery of T cells' negative regulators such as specific cell-surface receptors ... regulators, it has become possible to prevent the emergence of hypofunctional T cells. This review revisits ...

Abstract	While CAR-T and tgTCR-T therapies have exhibited noteworthy and promising outcomes in hematologic and solid tumors respectively, a set of distinct challenges remains. Consequently, the quest for novel strategies has become imperative to safeguard and more effectively release the full functions of engineered T cells. These factors are intricately linked to the success of adoptive cell therapy. Recently, CRISPR-based technologies have emerged as a major breakthrough for maintaining T cell functions. These technologies have allowed the discovery of T cells' negative regulators such as specific cell-surface receptors, cell-signaling proteins, and transcription factors that are involved in the development or maintenance of T cell dysfunction. By employing a CRISPR-genic invalidation approach to target these negative regulators, it has become possible to prevent the emergence of hypofunctional T cells. This review revisits the establishment of the dysfunctional profile of T cells before delving into a comprehensive summary of recent CRISPR-gene invalidations, with each invalidation contributing to the enhancement of engineered T cells' antitumor capacities. The narrative unfolds as we explore how these advancements were discovered and identified, marking a significant advancement in the pursuit of superior adoptive cell therapy.
Language	English
Publishing date	2024-04-12
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	1212513-1
ISSN	1476-5500 ; 0929-1903
ISSN (online)	1476-5500
ISSN	0929-1903
DOI	10.1038/s41417-024-00771-x
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Zs.A 4125: Show issues

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Article: Implications of Senescent T Cells for Cancer Immunotherapy.

Kasamatsu, Tetsuhiro

Cancers

2023 Volume 15, Issue 24

Abstract: ... responses to pathogens and tumor cells. In addition to aging, T-cell senescence is caused by repeated ... T) cells and general senescent T cells are largely similar. Senescent T cells demonstrate an increase ... associated secretory phenotypic factors, and metabolic reprogramming. Furthermore, senescent T cells ...

Abstract	T-cell senescence is thought to result from the age-related loss of the ability to mount effective responses to pathogens and tumor cells. In addition to aging, T-cell senescence is caused by repeated antigenic stimulation and chronic inflammation. Moreover, we demonstrated that T-cell senescence was induced by treatment with DNA-damaging chemotherapeutic agents. The characteristics of therapy-induced senescent T (TIS-T) cells and general senescent T cells are largely similar. Senescent T cells demonstrate an increase in the senescence-associated beta-galactosidase-positive population, cell cycle arrest, secretion of senescence-associated secretory phenotypic factors, and metabolic reprogramming. Furthermore, senescent T cells downregulate the expression of the co-stimulatory molecules CD27 and CD28 and upregulate natural killer cell-related molecules. Moreover, TIS-T cells showed increased PD-1 expression. However, the loss of proliferative capacity and decreased expression of co-stimulatory molecules associated with T-cell senescence cause a decrease in T-cell immunocompetence. In this review, we discuss the characteristics of senescent T-cells, including therapy-induced senescent T cells.
Language	English
Publishing date	2023-12-14
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers15245835
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