T cells in health and disease

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: June 19, 2023

T cells are crucial for immune functions to maintain health and prevent disease. cell development occurs in a stepwise process the thymus mainly generates CD4

Language: Английский

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γδ T cells: origin and fate, subsets, diseases and immunotherapy

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: Nov. 22, 2023

The intricacy of diseases, shaped by intrinsic processes like immune system exhaustion and hyperactivation, highlights the potential renormalization as a promising strategy in disease treatment. In recent years, our primary focus has centered on γδ T cell-based immunotherapy, particularly pioneering use allogeneic Vδ2

Language: Английский

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Gamma delta T-cell-based immune checkpoint therapy: attractive candidate for antitumor treatment

Molecular Cancer, Journal Year: 2023, Volume and Issue: 22(1)

Published: Feb. 15, 2023

Abstract As a nontraditional T-cell subgroup, γδT cells have gained popularity in the field of immunotherapy recent years. They extraordinary antitumor potential and prospects for clinical application. Immune checkpoint inhibitors (ICIs), which are efficacious tumor patients, become pioneer drugs since they were incorporated into practice. In addition, that infiltrated tissues found to be state exhaustion or anergy, there is upregulation many immune checkpoints (ICs) on their surface, suggesting similar ability respond ICIs as traditional effector T cells. Studies shown targeting ICs can reverse dysfunctional microenvironment (TME) exert effects by improving γδT-cell proliferation activation enhancing cytotoxicity. Clarification functional TME mechanisms underlying interaction with will solidify combined good treatment option.

Language: Английский

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CTLs heterogeneity and plasticity: implications for cancer immunotherapy

Molecular Cancer, Journal Year: 2024, Volume and Issue: 23(1)

Published: March 21, 2024

Cytotoxic T lymphocytes (CTLs) play critical antitumor roles, encompassing diverse subsets including CD4+, NK, and γδ cells beyond conventional CD8+ CTLs. However, definitive CTLs biomarkers remain elusive, as cytotoxicity-molecule expression does not necessarily confer cytotoxic capacity. differentiation involves transcriptional regulation by factors such T-bet Blimp-1, although epigenetic of is less clear. promote tumor killing through granules death receptor pathways, but may also stimulate tumorigenesis in some contexts. Given that cytotoxicity varies across tumors, enhancing this function critical. This review summarizes current knowledge on subsets, biomarkers, mechanisms, cancer-related functions, strategies for improving cytotoxicity. Key outstanding questions include refining the definition, characterizing subtype diversity, elucidating senescence delineating CTL-microbe relationships, enabling multi-omics profiling. A more comprehensive understanding biology will facilitate optimization their immunotherapy applications. Overall, synthesizes heterogeneity, regulation, functional enhancement immunity, highlighting gaps our control, microbial interactions, characterization. Addressing these refine immunology to better leverage functions against cancer.

Language: Английский

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Gamma/delta T cells as cellular vehicles for anti-tumor immunity

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 14

Published: Jan. 11, 2024

Adoptive cellular immunotherapy as a new paradigm to treat cancers is exemplified by the FDA approval of six chimeric antigen receptor-T cell therapies targeting hematological malignancies in recent years. Conventional αβ T cells applied these have proven efficacy but are confined almost exclusively autologous use. When infused into patients with mismatched human leukocyte antigen, recognize tissues such foreign and elicit devastating graft-versus-host disease. Therefore, one way overcome this challenge use naturally allogeneic immune types, γδ cells. occupy interface between innate adaptive immunity possess capacity detect wide variety ligands on transformed host In article, we review fundamental biology cells, including their subtypes, expression ligands, contrasting roles association cancer prognosis or survival, well discuss gaps knowledge pertaining type which currently endeavor elucidate. addition, propose how harness unique properties for based lessons gleaned from past clinical trials provide an update ongoing involving Lastly, elaborate strategies that been tested can be explored improve anti-tumor activity durability vivo.

Language: Английский

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Activated Chicken Gamma Delta T Cells Are Involved in Protective Immunity against Marek’s Disease

Viruses, Journal Year: 2023, Volume and Issue: 15(2), P. 285 - 285

Published: Jan. 19, 2023

Gamma delta (γδ) T cells play a significant role in the prevention of viral infection and tumor surveillance mammals. Although involvement γδ Marek’s disease virus (MDV) has been suggested, their detailed contribution to immunity against MDV or progression (MD) remains unknown. In current study, cell receptor (TCR)γδ-activated peripheral blood mononuclear (PBMCs) were infused into recipient chickens effects examined context formation by MDV. We demonstrated that adoptive transfer TCRγδ-activated PBMCs reduced replication lungs incidence MDV-challenged chickens. Infusion induced IFN-γ-producing at 10 days post-infection (dpi), degranulation activity circulating CD8α+ 21 dpi Additionally, upregulation IFN-γ granzyme A gene expression was spleen PBMCs-infused group compared control group. Taken together, our results revealed TCRγδ stimulation promotes effector function chicken cells, these may be involved protection MD.

Language: Английский

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Isolation and expansion of pure and functional γδ T cells

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Feb. 15, 2024

γδ T cells are important components of the immune system due to their ability elicit a fast and strong response against infected transformed cells. Because they can specifically effectively kill target in an MHC independent fashion, there is great interest utilize these anti-tumor therapies where antigen presentation may be hampered. Since only small fraction blood or tumor tissue cells, require extensive expansion allow for fundamental, preclinical ex vivo research. Although protocols successful, most based on depletion other cell types rather than specific isolation, resulting unpredictable purity isolated fraction. Moreover, primary focus lies with Vδ2 + while Vδ1 likewise have potential. Here, we investigated whether directly from could efficiently expanded maintaining function. subsets were using MACS separation, followed by FACS sorting, yielding >99% pure Isolated expand immediately after isolation upon freeze/thawing reached ratios between 200 2000-fold starting varying numbers cytokine supported feeder stimulations. MACS/FACS PHA stimulated as good immobilized antibody mediated PBMCs, but delivered purer After expansion, potential effector functions demonstrated IFN-γ, TNF-α granzyme B production PMA/ionomycin stimulation effective killing capacity multiple lines was confirmed assays. In conclusion, productively low suggesting that this protocol even extracted biopsies.

Language: Английский

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γδ T Are Significantly Impacted by CLL Burden but Only Mildly Influenced by M-MDSCs

Cancers, Journal Year: 2025, Volume and Issue: 17(2), P. 254 - 254

Published: Jan. 14, 2025

Background/Objectives. The current study explores the impact of CLL on γδ T cells and, in an attempt to better understand sources immunosuppression, assesses M-MDSCs vitro. Methods. included 163 patients and 34 healthy volunteers. were screened with flow cytometry, including NKG2D, Fas, FasL, TRAIL staining. Additionally, deepen understanding immunosuppressive T, a set vitro co-cultures was performed. Results. RNAseq revealed significant, though relatively minor, changes transcriptome. Functional analyses showed minor drop cytotoxic potential against cells. Finally, depletion from CLL-derived peripheral blood mononuclear did not restore cells’ proliferative response. Conclusions. Altogether, this suggests activated T. Thus, it seems probable that other mechanisms than mediate negative circulating

Language: Английский

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Synthesis and Evaluation of Triazole-Containing Aryl/Acyloxy Prodrugs of a BTN3A1 Ligand

European Journal of Medicinal Chemistry, Journal Year: 2025, Volume and Issue: 287, P. 117345 - 117345

Published: Feb. 1, 2025

Language: Английский

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A comprehensive pan-cancer examination of transcription factor MAFF: Oncogenic potential, prognostic relevance, and immune landscape dynamics

International Immunopharmacology, Journal Year: 2025, Volume and Issue: 149, P. 114105 - 114105

Published: Feb. 8, 2025

Language: Английский

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