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Article ; Online: Harnessing Chimeric Antigen Receptor-engineered Invariant Natural Killer T Cells: Therapeutic Strategies for Cancer and the Tumor Microenvironment.

Wang, Yiqing / Li, Yan-Ruide

2024

Abstract: Chimeric antigen receptor (CAR)-engineered T (CAR-T) cell therapy has emerged as a revolutionary approach for cancer treatment, especially for hematologic cancers. However, CAR-T therapy has some limitations, including cytokine release syndrome (CRS), ... ...

Abstract	Chimeric antigen receptor (CAR)-engineered T (CAR-T) cell therapy has emerged as a revolutionary approach for cancer treatment, especially for hematologic cancers. However, CAR-T therapy has some limitations, including cytokine release syndrome (CRS), immune cellassociated neurologic syndrome (ICANS), and difficulty in targeting solid tumors and delivering allogeneic cell therapy due to graft-versus-host disease (GvHD). Therefore, it is important to explore other cell sources for CAR engineering. Invariant natural killer T (iNKT) cells are a potential target, as they possess powerful antitumor ability and do not recognize mismatched major histocompatibility complexes (MHCs) and protein antigens, thus avoiding the risk of GvHD. CAR-engineered iNKT (CAR-iNKT) cell therapy offers a promising new approach to cancer immunotherapy by overcoming the drawbacks of CAR-T cell therapy while retaining potent antitumor capabilities. This review summarizes the current CAR-iNKT cell products, their functions and phenotypes, and their potential for off-the-shelf cancer immunotherapy.
Language	English
Publishing date	2024-01-16
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2132197-8
ISSN	1873-4316 ; 1389-2010
ISSN (online)	1873-4316
ISSN	1389-2010
DOI	10.2174/0113892010265228231116073012
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Article ; Online: Immune evasion in cell-based immunotherapy: unraveling challenges and novel strategies.

Li, Yan-Ruide / Halladay, Tyler / Yang, Lili

Journal of biomedical science

2024 Volume 31, Issue 1, Page(s) 5

Abstract: Cell-based immunotherapies (CBIs), notably exemplified by chimeric antigen receptor (CAR)-engineered T (CAR-T) cell therapy, have emerged as groundbreaking approaches for cancer therapy. Nevertheless, akin to various other therapeutic modalities, tumor ... ...

Abstract	Cell-based immunotherapies (CBIs), notably exemplified by chimeric antigen receptor (CAR)-engineered T (CAR-T) cell therapy, have emerged as groundbreaking approaches for cancer therapy. Nevertheless, akin to various other therapeutic modalities, tumor cells employ counterstrategies to manifest immune evasion, thereby circumventing the impact of CBIs. This phenomenon is facilitated by an intricately immunosuppression entrenched within the tumor microenvironment (TME). Principal mechanisms underpinning tumor immune evasion from CBIs encompass loss of antigens, downregulation of antigen presentation, activation of immune checkpoint pathways, initiation of anti-apoptotic cascades, and induction of immune dysfunction and exhaustion. In this review, we delve into the intrinsic mechanisms underlying the capacity of tumor cells to resist CBIs and proffer prospective stratagems to navigate around these challenges.
MeSH term(s)	Humans ; Receptors, Chimeric Antigen/metabolism ; Immune Evasion ; Prospective Studies ; Immunotherapy, Adoptive ; Immunotherapy ; Tumor Microenvironment ; Neoplasms/therapy
Chemical Substances	Receptors, Chimeric Antigen
Language	English
Publishing date	2024-01-12
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	1193378-1
ISSN	1423-0127 ; 1021-7770
ISSN (online)	1423-0127
ISSN	1021-7770
DOI	10.1186/s12929-024-00998-8
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Article ; Online: Target tumor microenvironment by innate T cells.

Li, Yan-Ruide / Wilson, Matthew / Yang, Lili

Frontiers in immunology

2022 Volume 13, Page(s) 999549

Abstract: The immunosuppressive tumor microenvironment (TME) remains one of the most prevailing barriers obstructing the implementation of effective immunotherapy against solid-state cancers. Eminently composed of immunosuppressive tumor associated macrophages ( ... ...

Abstract	The immunosuppressive tumor microenvironment (TME) remains one of the most prevailing barriers obstructing the implementation of effective immunotherapy against solid-state cancers. Eminently composed of immunosuppressive tumor associated macrophages (TAMs) and myeloid-derived suppressor cells (MDSCs) among others, the TME attenuates the effects of immune checkpoint blockade and adoptive cell therapies, mandating a novel therapy capable of TME remediation. In this review we explore the potential of three innate-like T cell subsets, invariant natural killer T (iNKT), mucosal-associated invariant T (MAIT) cells, and gamma delta T (γδT) cells, that display an intrinsic anti-TAM/MDSC capacity. Exhibiting both innate and adaptive properties, innate-like T cell types express a subset-specific TCR with distinct recombination, morphology, and target cell recognition, further supplemented by a variety of NK activating receptors. Both NK activating receptor and TCR activation result in effector cell cytotoxicity against targeted immunosuppressive cells for TME remediation. In addition, innate-like T cells showcase moderate levels of tumor cell killing, providing dual antitumor and anti-TAM/MDSC function. This latent antitumor capacity can be further bolstered by chimeric antigen receptor (CAR) engineering for recognition of tumor specific antigens to enhance antitumor targeting. In contrast with established CAR-T cell therapies, adoption of these innate-like cell types provides an enhanced safety profile without the risk of graft versus host disease (GvHD), due to their non-recognition of mismatched major histocompatibility complex (MHC) molecules, for use as widely accessible, allogeneic "off-the-shelf" cancer immunotherapy.
MeSH term(s)	Tumor Microenvironment ; Receptors, Chimeric Antigen/metabolism ; Immune Checkpoint Inhibitors ; Immunotherapy ; Immunotherapy, Adoptive
Chemical Substances	Receptors, Chimeric Antigen ; Immune Checkpoint Inhibitors
Language	English
Publishing date	2022-10-06
Publishing country	Switzerland
Document type	Journal Article ; Review ; 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.2022.999549
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Article ; Online: Graft-versus-Host Disease Modulation by Innate T Cells.

Fang, Ying / Zhu, Yichen / Kramer, Adam / Chen, Yuning / Li, Yan-Ruide / Yang, Lili

International journal of molecular sciences

2023 Volume 24, Issue 4

Abstract: Allogeneic cell therapies, defined by genetically mismatched transplantation, have the potential to become a cost-effective solution for cell-based cancer immunotherapy. However, this type of therapy is often accompanied by the development of graft- ... ...

Abstract	Allogeneic cell therapies, defined by genetically mismatched transplantation, have the potential to become a cost-effective solution for cell-based cancer immunotherapy. However, this type of therapy is often accompanied by the development of graft-versus-host disease (GvHD), induced by the mismatched major histocompatibility complex (MHC) between healthy donors and recipients, leading to severe complications and death. To address this issue and increase the potential for allogeneic cell therapies in clinical practice, minimizing GvHD is a crucial challenge. Innate T cells, encompassing subsets of T lymphocytes including mucosal-associated invariant T (MAIT) cells, invariant natural killer T (iNKT) cells, and gamma delta T (γδ T) cells, offer a promising solution. These cells express MHC-independent T-cell receptors (TCRs), allowing them to avoid MHC recognition and thus GvHD. This review examines the biology of these three innate T-cell populations, evaluates research on their roles in GvHD modulation and allogeneic stem cell transplantation (allo HSCT), and explores the potential futures for these therapies.
MeSH term(s)	Humans ; Hematopoietic Stem Cell Transplantation/adverse effects ; Graft vs Host Disease/etiology ; Mucosal-Associated Invariant T Cells ; Natural Killer T-Cells ; Immunotherapy/adverse effects
Language	English
Publishing date	2023-02-17
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms24044084
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Article ; Online: Exploring the dynamic interplay between cancer stem cells and the tumor microenvironment: implications for novel therapeutic strategies.

Li, Yan-Ruide / Fang, Ying / Lyu, Zibai / Zhu, Yichen / Yang, Lili

Journal of translational medicine

2023 Volume 21, Issue 1, Page(s) 686

Abstract: Cancer stem cells (CSCs) have emerged as key contributors to tumor initiation, growth, and metastasis. In addition, CSCs play a significant role in inducing immune evasion, thereby compromising the effectiveness of cancer treatments. The reciprocal ... ...

Abstract	Cancer stem cells (CSCs) have emerged as key contributors to tumor initiation, growth, and metastasis. In addition, CSCs play a significant role in inducing immune evasion, thereby compromising the effectiveness of cancer treatments. The reciprocal communication between CSCs and the tumor microenvironment (TME) is observed, with the TME providing a supportive niche for CSC survival and self-renewal, while CSCs, in turn, influence the polarization and persistence of the TME, promoting an immunosuppressive state. Consequently, these interactions hinder the efficacy of current cancer therapies, necessitating the exploration of novel therapeutic approaches to modulate the TME and target CSCs. In this review, we highlight the intricate strategies employed by CSCs to evade immune surveillance and develop resistance to therapies. Furthermore, we examine the dynamic interplay between CSCs and the TME, shedding light on how this interaction impacts cancer progression. Moreover, we provide an overview of advanced therapeutic strategies that specifically target CSCs and the TME, which hold promise for future clinical and translational studies in cancer treatment.
MeSH term(s)	Humans ; Neoplasms/pathology ; Immunotherapy ; Cell Transformation, Neoplastic ; Neoplastic Stem Cells/pathology ; Tumor Microenvironment
Language	English
Publishing date	2023-10-02
Publishing country	England
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	2118570-0
ISSN	1479-5876 ; 1479-5876
ISSN (online)	1479-5876
ISSN	1479-5876
DOI	10.1186/s12967-023-04575-9
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Article ; Online: Advancing cell-based cancer immunotherapy through stem cell engineering.

Li, Yan-Ruide / Dunn, Zachary Spencer / Yu, Yanqi / Li, Miao / Wang, Pin / Yang, Lili

Cell stem cell

2023 Volume 30, Issue 5, Page(s) 592–610

Abstract: Advances in cell-based therapy, particularly CAR-T cell therapy, have transformed the treatment of hematological malignancies. Although an important step forward for the field, autologous CAR-T therapies are hindered by high costs, manufacturing ... ...

Abstract	Advances in cell-based therapy, particularly CAR-T cell therapy, have transformed the treatment of hematological malignancies. Although an important step forward for the field, autologous CAR-T therapies are hindered by high costs, manufacturing challenges, and limited efficacy against solid tumors. With ongoing progress in gene editing and culture techniques, engineered stem cells and their application in cell therapy are poised to address some of these challenges. Here, we review stem cell-based immunotherapy approaches, stem cell sources, gene engineering and manufacturing strategies, therapeutic platforms, and clinical trials, as well as challenges and future directions for the field.
MeSH term(s)	Humans ; Receptors, Chimeric Antigen/genetics ; Immunotherapy ; Immunotherapy, Adoptive/methods ; Neoplasms/therapy ; Cell Engineering
Chemical Substances	Receptors, Chimeric Antigen
Language	English
Publishing date	2023-03-21
Publishing country	United States
Document type	Journal Article ; Review ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2375354-7
ISSN	1875-9777 ; 1934-5909
ISSN (online)	1875-9777
ISSN	1934-5909
DOI	10.1016/j.stem.2023.02.009
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Zs.A 6589: 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)
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Article: Immune aspects of the bi-directional neuroimmune facilitator TRPV1

Li, Yan-Ruide / Gupta, Puneet

Molecular biology reports. 2019 Feb., v. 46, no. 1

2019

Abstract: A rapidly growing area of interest in biomedical science involves the reciprocal crosstalk between the sensory nervous and immune systems. Both of these systems are highly integrated, detecting potential environmental harms and restoring homeostasis. ... ...

Abstract	A rapidly growing area of interest in biomedical science involves the reciprocal crosstalk between the sensory nervous and immune systems. Both of these systems are highly integrated, detecting potential environmental harms and restoring homeostasis. Many different cytokines, receptors, neuropeptides, and other proteins are involved in this bidirectional communication that are common to both systems. One such family of proteins includes the transient receptor potential vanilloid (TRPV) proteins. Though much progress has been made in understanding TRPV proteins in the nervous system, their functions in the immune system are not well elucidated. Hence, further understanding their role in the peripheral immune system and as regulators of neuroimmunity is critical for evaluating their potential as therapeutic targets for numerous inflammatory disorders, cancers, and other disease states. Here, we focus on the latest advancements in understanding TRPV1 and TRPV2’s roles in the immune system, TRPV1 in neuroimmunity, and TRPV1’s potential involvement in anti-tumor therapy.
Keywords	biomedical research ; cytokines ; homeostasis ; immune system ; neoplasms ; nervous system ; neuropeptides ; receptors ; therapeutics ; transient receptor potential vanilloid channels
Language	English
Dates of publication	2019-02
Size	p. 1499-1510.
Publishing place	Springer Netherlands
Document type	Article
Note	Review
ZDB-ID	186544-4
ISSN	1573-4978 ; 0301-4851
ISSN (online)	1573-4978
ISSN	0301-4851
DOI	10.1007/s11033-018-4560-6
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Upf proteins: highly conserved factors involved in nonsense mRNA mediated decay.

Gupta, Puneet / Li, Yan-Ruide

Molecular biology reports

2018 Volume 45, Issue 1, Page(s) 39–55

Abstract: Over 10% of genetic diseases are caused by mutations that introduce a premature termination codon in protein-coding mRNA. Nonsense-mediated mRNA decay (NMD) is an essential cellular pathway that degrades these mRNAs to prevent the accumulation of harmful ...

Abstract	Over 10% of genetic diseases are caused by mutations that introduce a premature termination codon in protein-coding mRNA. Nonsense-mediated mRNA decay (NMD) is an essential cellular pathway that degrades these mRNAs to prevent the accumulation of harmful partial protein products. NMD machinery is also increasingly appreciated to play a role in other essential cellular functions, including telomere homeostasis and the regulation of normal mRNA turnover, and is misregulated in numerous cancers. Hence, understanding and designing therapeutics targeting NMD is an important goal in biomedical science. The central regulator of NMD, the Upf1 protein, interacts with translation termination factors and contextual factors to initiate NMD specifically on mRNAs containing PTCs. The molecular details of how these contextual factors affect Upf1 function remain poorly understood. Here, we review plausible models for the NMD pathway and the evidence for the variety of roles NMD machinery may play in different cellular processes.
MeSH term(s)	Carrier Proteins/genetics ; Codon, Nonsense/genetics ; Codon, Nonsense/physiology ; Humans ; Mutation ; Nonsense Mediated mRNA Decay/physiology ; Protein Biosynthesis ; RNA Helicases/metabolism ; RNA Helicases/physiology ; RNA Stability/physiology ; RNA, Messenger/genetics ; Trans-Activators/genetics ; Trans-Activators/metabolism ; Trans-Activators/physiology ; Transcription Factors/genetics ; Transcription Factors/metabolism ; Transcription Factors/physiology
Chemical Substances	Carrier Proteins ; Codon, Nonsense ; RNA, Messenger ; Trans-Activators ; Transcription Factors ; RNA Helicases (EC 3.6.4.13) ; UPF1 protein, human (EC 3.6.4.13)
Language	English
Publishing date	2018-02
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	186544-4
ISSN	1573-4978 ; 0301-4851
ISSN (online)	1573-4978
ISSN	0301-4851
DOI	10.1007/s11033-017-4139-7
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Article ; Online: Immune aspects of the bi-directional neuroimmune facilitator TRPV1.

Li, Yan-Ruide / Gupta, Puneet

Molecular biology reports

2018 Volume 46, Issue 1, Page(s) 1499–1510

Abstract	A rapidly growing area of interest in biomedical science involves the reciprocal crosstalk between the sensory nervous and immune systems. Both of these systems are highly integrated, detecting potential environmental harms and restoring homeostasis. Many different cytokines, receptors, neuropeptides, and other proteins are involved in this bidirectional communication that are common to both systems. One such family of proteins includes the transient receptor potential vanilloid (TRPV) proteins. Though much progress has been made in understanding TRPV proteins in the nervous system, their functions in the immune system are not well elucidated. Hence, further understanding their role in the peripheral immune system and as regulators of neuroimmunity is critical for evaluating their potential as therapeutic targets for numerous inflammatory disorders, cancers, and other disease states. Here, we focus on the latest advancements in understanding TRPV1 and TRPV2's roles in the immune system, TRPV1 in neuroimmunity, and TRPV1's potential involvement in anti-tumor therapy.
MeSH term(s)	Animals ; Humans ; Immune System/metabolism ; Models, Biological ; Neoplasms/immunology ; Nervous System/immunology ; TRPV Cation Channels/metabolism
Chemical Substances	TRPV Cation Channels
Language	English
Publishing date	2018-12-15
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	186544-4
ISSN	1573-4978 ; 0301-4851
ISSN (online)	1573-4978
ISSN	0301-4851
DOI	10.1007/s11033-018-4560-6
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Article ; Online: Engineering stem cells for cancer immunotherapy.

Li, Yan-Ruide / Zhou, Yang / Kramer, Adam / Yang, Lili

Trends in cancer

2021 Volume 7, Issue 12, Page(s) 1059–1073

Abstract: Engineering stem cells presents an attractive paradigm for cancer immunotherapy. Stem cells engineered to stably express various chimeric antigen receptors (CARs) or T-cell receptors (TCRs) against tumor-associated antigens are showing increasing promise ...

Abstract	Engineering stem cells presents an attractive paradigm for cancer immunotherapy. Stem cells engineered to stably express various chimeric antigen receptors (CARs) or T-cell receptors (TCRs) against tumor-associated antigens are showing increasing promise in the treatment of solid tumors and hematologic malignancies. Stem cells engraft for long-term immune cell generation and serve as a sustained source of tumor-specific effector cells to maintain remissions. Furthermore, engineering stem cells provides 'off-the-shelf' cellular products, obviating the need for a personalized and patient-specific product that plagues current autologous cell therapies. Herein, we summarize recent progress of stem cell-engineered cancer therapies, and discuss the utility, impact, opportunities, and challenges of cellular engineering that may facilitate the translational and clinical research.
MeSH term(s)	Genetic Engineering ; Humans ; Immunotherapy ; Immunotherapy, Adoptive ; Killer Cells, Natural ; Neoplasms/therapy ; Stem Cells
Language	English
Publishing date	2021-09-01
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2852626-0
ISSN	2405-8025 ; 2405-8033 ; 2405-8033
ISSN (online)	2405-8025 ; 2405-8033
ISSN	2405-8033
DOI	10.1016/j.trecan.2021.08.004
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