Dual Effect of Immune Cells within Tumour Microenvironment: Pro- and Anti-Tumour Effects and Their Triggers

Cancers, Journal Year: 2022, Volume and Issue: 14(7), P. 1681 - 1681

Published: March 25, 2022

Our body is constantly exposed to pathogens or external threats, but with the immune response that our can develop, we fight off and defeat possible attacks infections. Nevertheless, sometimes this threat comes from an internal factor. Situations such as existence of a tumour also cause system (IS) be put on alert. Indeed, link between immunology cancer evident these days, IS being used one important targets for treating cancer. able eliminate those abnormal damaged cells found in body, preventing uncontrolled proliferation lead However, several cases, escape IS. It has been observed cells, extracellular matrix, blood vessels, fat various molecules could support growth development. Thus, developing receives structural support, irrigation energy, among other resources, making its survival progression possible. All components accompany help survive grow are called microenvironment (TME). Given importance presence development process, review will focus TME: cells. Immune anti-tumour protecting us against cells; nevertheless, they behave pro-tumoural thus promoting survival. In review, pro-tumour immunity discussed. addition, TME influence dual effect analysed.

Language: Английский

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Gamma Delta T-Cell Based Cancer Immunotherapy: Past-Present-Future

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: June 16, 2022

γδ T-cells directly recognize and kill transformed cells independently of HLA-antigen presentation, which makes them a highly promising effector cell compartment for cancer immunotherapy. Novel T-cell-based immunotherapies, primarily focusing on the two major T-cell subtypes that infiltrate tumors ( i.e. Vδ1 Vδ2), are being developed. The subset is enriched in tissues contains both as well regulatory with tumor-promoting potential. Vδ2 T-cells, contrast, circulation consist large, relatively homogeneous, pro-inflammatory subset. Healthy individuals typically harbor order 50-500 million Vγ9Vδ2 peripheral blood alone (1-10% total CD3 + population), can rapidly expand upon stimulation. receptor senses intracellular phosphorylated metabolites, accumulate result mevalonate pathway dysregulation or pharmaceutical intervention. Early clinical studies investigating therapeutic potential were based either ex vivo expansion adoptive transfer their systemic activation aminobisphosphonates synthetic phosphoantigens, combined low dose IL-2. Immune-related adverse events (irAE) generally \mild, but efficacy these approaches provided overall limited benefit. In recent years, critical advances have renewed excitement Here, we review strategies discuss prospects those currently evaluated patients future therapies might arise from current pre-clinical results.

Language: Английский

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Chimeric antigen receptor- and natural killer cell receptor-engineered innate killer cells in cancer immunotherapy

Cellular and Molecular Immunology, Journal Year: 2021, Volume and Issue: 18(9), P. 2083 - 2100

Published: July 15, 2021

Language: Английский

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Advances in NK cell production

Cellular and Molecular Immunology, Journal Year: 2022, Volume and Issue: 19(4), P. 460 - 481

Published: Jan. 5, 2022

Language: Английский

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Targeting Immunosuppressive Tumor-Associated Macrophages Using Innate T Cells for Enhanced Antitumor Reactivity

Cancers, Journal Year: 2022, Volume and Issue: 14(11), P. 2749 - 2749

Published: June 1, 2022

The field of T cell-based and chimeric antigen receptor (CAR)-engineered (CAR-T) antitumor immunotherapy has seen substantial developments in the past decade; however, considerable issues, such as graft-versus-host disease (GvHD) tumor-associated immunosuppression, have proven to be roadblocks widespread adoption implementation. Recent innate immune CAR therapy opened several doors for expansion this therapy, especially it relates allogeneic cell sources solid tumor infiltration. This study establishes vitro killing assays examine TAM-targeting efficacy MAIT, iNKT, γδT cells. also assesses ability CAR-engineered cells, evaluating their potential clinical therapies. trials presented demonstrate TAM-killing abilities all three types, confirm enhanced tumor- capacity these cells suggest that supplements cytotoxicity with remediation microenvironment (TME)-immunosuppression.

Language: Английский

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A close look at current γδ T-cell immunotherapy

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: March 31, 2023

Owing to their antitumor and major histocompatibility complex (MHC)-independent capacities, γδ T cells have gained popularity in adoptive T-cell immunotherapy recent years. However, many unknowns still exist regarding cells, few clinical data been collected. Therefore, this review aims describe all the main features of applications provide a systematic view current immunotherapy. Specifically, will focus on how performed treating cancers clinics, trials that conducted date, role pharmaceutical industry.

Language: Английский

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Biomarkers for response to TIL therapy: a comprehensive review

Journal for ImmunoTherapy of Cancer, Journal Year: 2024, Volume and Issue: 12(3), P. e008640 - e008640

Published: March 1, 2024

Adoptive cell therapy with tumor-infiltrating lymphocytes (TIL) has demonstrated durable clinical responses in patients metastatic melanoma, substantiated by recent positive results of the first phase III trial on TIL therapy. Being a demanding and logistically complex treatment, extensive preclinical effort is required to optimize patient selection identifying predictive biomarkers response. This review aims comprehensively summarize current evidence regarding potential impact tumor-related factors (such as mutational burden, neoantigen load, immune infiltration, status oncogenic driver genes, epigenetic modifications), characteristics (including disease burden location, baseline cytokines lactate dehydrogenase serum levels, human leucocyte antigen haplotype, or prior exposure checkpoint inhibitors other anticancer therapies), phenotypic features transferred T cells (mainly total count, CD8:CD4 ratio, ex vivo culture time, expression exhaustion markers, costimulatory signals, antitumor reactivity, scope target tumor-associated antigens), treatment-related lymphodepleting chemotherapy postinfusion administration interleukin-2).

Language: Английский

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GD2-targeting therapy: a comparative analysis of approaches and promising directions

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

Published: March 15, 2024

Disialoganglioside GD2 is a promising target for immunotherapy with expression primarily restricted to neuroectodermal and epithelial tumor cells. Although its role in the maintenance repair of neural tissue well-established, functions during normal organism development remain understudied. Meanwhile, studies have shown that plays an important tumorigenesis. Its include proliferation, invasion, motility, metastasis, high ability transform microenvironment may be associated malignant phenotype. Structurally, glycosphingolipid stably expressed on surface cells, making it suitable candidate targeting by antibodies or chimeric antigen receptors. Based mouse monoclonal antibodies, humanized their combinations cytokines, toxins, drugs, radionuclides, nanoparticles as well receptor been developed. Furthermore, vaccines photoimmunotherapy are being used treat GD2-positive tumors, aptamers can targeting. In field cell therapy, allogeneic immunocompetent cells also utilized enhance therapy. Efforts currently made optimize modifying design transducing not only αβ T but γδ NK NKT macrophages. addition, combine both diagnostic therapeutic methods, allowing early detection disease minimal residual disease. This review discusses each method strategy, advantages disadvantages, highlights future directions

Language: Английский

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Allogeneic gamma delta T cells as adoptive cellular therapy for hematologic malignancies

Exploration of Immunology, Journal Year: 2022, Volume and Issue: unknown, P. 334 - 350

Published: June 7, 2022

Cancer immunotherapy, especially T-cell driven targeting, has significantly evolved and improved over the past decade, paving way to treat previously refractory cancers. Hematologic malignancies, given their direct tumor accessibility less immunosuppressive microenvironment compared solid tumors, are better suited be targeted by cellular immunotherapies. Gamma delta (γδ) T cells, with unique attributes spanning entirety of immune system, make a tantalizing therapeutic platform for cancer immunotherapy. Their inherent anti-tumor properties, ability act like antigen-presenting advantage having no major histocompatibility complex (MHC) restrictions, allow greater flexibility in utility target αβ cell counterpart. MHC-independent activity, coupled easily expanded from peripheral blood, enhance potential used as an allogeneic product. In this review, utilizing γδ cells hematologic malignancies is described, specific focus on applicability adoptive therapy

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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