Antigen-Presenting Cell Characteristics of Human γδ T Lymphocytes in Chronic Myeloid Leukemia

Sawaisorn, Piamsiri; Tangchaikeeree, Tienrat; Chan-On, Waraporn; Leepiyasakulchai, Chaniya; Udomsangpetch, Rachanee; Hongeng, Suradej; Jangpatarapongsa, Kulachart

doi:10.1080/08820139.2018.1529039

Cited by 9 publications

(5 citation statements)

References 35 publications

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“…The APC-like phenotype and function of Vg9Vd2 T cells have been confirmed in clinical trials. 44 CAR-grafted Vg9Vd2 T cells would retain the APC ability to take up tumor antigens and cross present the processed peptides to conventional CD4 + and CD8 + ab T cells. 45 Therefore, it is important to recognize that Vg9Vd2 T cells may mediate systemic immunity and provide indirect antitumor effects in cancer patients.…”

Section: Discussionmentioning

confidence: 99%

Electroporation of NKG2D RNA CAR Improves Vγ9Vδ2 T Cell Responses against Human Solid Tumor Xenografts

Ang

Xiao

et al. 2020

Molecular Therapy - Oncolytics

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Vg9Vd2 T cell-based anticancer immunotherapy has shown some promise in early-phase clinical trials but there is still large room for improvement. Using the extracellular domain of the human NKG2D, a stimulatory receptor expressed by Vg9Vd2 T cells, we constructed NKG2D ligand-specific chimeric antigen receptors (CARs). We adopted a non-viral CAR approach via mRNA electroporation to modify Vg9Vd2 T cells and demonstrated that, upon interaction with the NKG2D ligand-positive cancer cells, the CARs substantially enhanced the cytotoxic activity of the modified cells toward multiple cultured solid tumor cell lines, including those resistant to Zometa treatment. Repeated doses of the CAR-expressing cells resulted in tumor regression in mice with established tumors, extending median survival time by up to 132% as compared to the PBS control group. The findings suggest clinical potential for RNA CAR-modified Vg9Vd2 T cells to treat a wide variety of NKG2D ligand-expressing cancers.

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Section: Discussionmentioning

confidence: 99%

Electroporation of NKG2D RNA CAR Improves Vγ9Vδ2 T Cell Responses against Human Solid Tumor Xenografts

Ang

Xiao

et al. 2020

Molecular Therapy - Oncolytics

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“…Functionally, γδ T cells can be rapidly activated by specific receptor–ligand interactions [ 7 ], upon which they possess the capacity for clonal expansion and provide a major source of cytokine and chemokine production [ 18 , 19 , 20 , 21 ]. This facilitates their abilities to exert direct or indirect immune responses by functioning as professional antigen presenting cells (APCs) [ 22 , 23 ], providing T- and B-cell helper functions [ 24 ] or directly killing compromised cells [ 25 , 26 , 27 ]. Importantly, γδ T cells can rapidly respond to specific ligand types that are not recognised by other immune cells, where stress signal recognition by γδ T cells as one example in particular is critical for the immune detection of many cancers [ 28 , 29 ].…”

Section: Introductionmentioning

confidence: 99%

The Diverse Roles of γδ T Cells in Cancer: From Rapid Immunity to Aggressive Lymphoma

Schönefeldt

Wais

Herling

et al. 2021

Cancers

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γδ T cells are unique players in shaping immune responses, lying at the intersection between innate and adaptive immunity. Unlike conventional αβ T cells, γδ T cells largely populate non-lymphoid peripheral tissues, demonstrating tissue specificity, and they respond to ligands in an MHC-independent manner. γδ T cells display rapid activation and effector functions, with a capacity for cytotoxic anti-tumour responses and production of inflammatory cytokines such as IFN-γ or IL-17. Their rapid cytotoxic nature makes them attractive cells for use in anti-cancer immunotherapies. However, upon transformation, γδ T cells can give rise to highly aggressive lymphomas. These rare malignancies often display poor patient survival, and no curative therapies exist. In this review, we discuss the diverse roles of γδ T cells in immune surveillance and response, with a particular focus on cancer immunity. We summarise the intriguing dichotomy between pro- and anti-tumour functions of γδ T cells in solid and haematological cancers, highlighting the key subsets involved. Finally, we discuss potential drivers of γδ T-cell transformation, summarising the main γδ T-cell lymphoma/leukaemia entities, their clinical features, recent advances in mapping their molecular and genomic landscapes, current treatment strategies and potential future targeting options.

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“…This means that the same quantitative response could have a range of biological explanations: a few cells being completely ruptured, many cells becoming slightly leaky or a mix of ruptured and leaky cells. For cells that grow in suspension, multiple FACS analysis methods for the assessment of cytotoxicity exist ( Jedema et al, 2004 ; Kim et al, 2007 ; Sawaisorn et al, 2019 ), but for adherent cells a FACS approach is less common. We have demonstrated that FACS is also an excellent methodology for assessing Vγ9Vδ2 T cell cytotoxicity towards adherent cells.…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, the same numerical response could originate from widely different combinations of live, damaged and dead cells. For target cells that grow in suspension, FACS-based cytotoxicity methods are frequently used ( Cosan et al, 2017 ; Jedema et al, 2004 ; Lecoeur et al, 2001 ; Sawaisorn et al, 2019 ), but for adherent target cells this approach is rare. FACS-based cytotoxicity assays are based on the differential staining of mostly intact dead versus live cells, but is unable to account for cells that disintegrate.…”

Section: Introductionmentioning

confidence: 99%

Potentiating Vγ9Vδ2 T cell proliferation and assessing their cytotoxicity towards adherent cancer cells at the single cell level

et al. 2022

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Vγ9Vδ2 T cells is the dominant γδ T cell subset in human blood. They are cytotoxic and activated by phosphoantigens whose concentrations are increased in cancer cells, making the cancer cells targets for Vγ9Vδ2 T cell immunotherapy. For successful immunotherapy, it is important both to characterise Vγ9Vδ2 T cell proliferation and optimise the assessment of their cytotoxic potential, which is the aim of this study. We found that supplementation with freshly-thawed human serum potentiated Vγ9Vδ2 T cell proliferation from peripheral mononuclear cells (PBMCs) stimulated with (E)-4-Hydroxy-3-methyl-but-2-enyl diphosphate (HMBPP) and consistently enabled Vγ9Vδ2 T cell proliferation from cryopreserved PBMCs. In cryopreserved PBMCs the proliferation was higher than in freshly prepared PBMCs. In a panel of short-chain prenyl alcohols, monophosphates and diphosphates, most diphosphates and also dimethylallyl monophosphate stimulated Vγ9Vδ2 T cell proliferation. We developed a method where the cytotoxicity of Vγ9Vδ2 T cells towards adherent cells is assessed at the single cell level using flow cytometry, which gives more clear-cut results than the traditional bulk release assays. Moreover, we found that HMBPP enhances the Vγ9Vδ2 T cell cytotoxicity towards colon cancer cells. In summary we have developed an easily interpretable method to assess the cytotoxicity of Vγ9Vδ2 T cells towards adherent cells, found that Vγ9Vδ2 T cell proliferation can be potentiated media-supplementation and how misclassification of non-responders may be avoided. Our findings will be useful in the further development of Vγ9Vδ2 T cell immunotherapy.

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Antigen-Presenting Cell Characteristics of Human γδ T Lymphocytes in Chronic Myeloid Leukemia

Cited by 9 publications

References 35 publications

Electroporation of NKG2D RNA CAR Improves Vγ9Vδ2 T Cell Responses against Human Solid Tumor Xenografts

Electroporation of NKG2D RNA CAR Improves Vγ9Vδ2 T Cell Responses against Human Solid Tumor Xenografts

The Diverse Roles of γδ T Cells in Cancer: From Rapid Immunity to Aggressive Lymphoma

Potentiating Vγ9Vδ2 T cell proliferation and assessing their cytotoxicity towards adherent cancer cells at the single cell level

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