Flow cytometric assessment of autologous γδ T cells in patients with acute myeloid leukemia: Potential effector cells for immunotherapy?

Aswald, J.; Wang, Xinghua; Aswald, S.; Lutynski, Andrzej; Minden, Mark D.; Messner, Hans A.; Keating, Armand

doi:10.1002/cyto.b.20115

Cited by 14 publications

(12 citation statements)

References 73 publications

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“…1). Given the fact that the presence of activated gd T cells in cancer patients is associated with a beneficial outcome 16,[22][23][24] , monitoring gd T cells would be an interesting parameter for evaluation of DC vaccines.…”

Section: Discussionmentioning

confidence: 99%

“…14,15 Furthermore, gd T cells are considered to be important players in cancer immune surveillance. 2 This is, among other things, substantiated by (I) their overrepresentation in reactive lymphatic regions associated with neoplasia, 16 (II) their potential to kill a variety of tumor cells including bladder cancer, 17 colon cancer, 18 glioblastoma multiforme, 19 hematological malignancies 20 and multiple myeloma, 21 and (III) the observed trend between the presence of activated gd T cells in cancer patients and a beneficial outcome. [22][23][24] gd T cells dispose of a sensitive ability to distinguish "foreign" or transformed cells from healthy self-cells, using activating receptors and inhibitory killer Ig-like receptors ( Table 1).…”

Section: Gd T Cells and Cancer Immunitymentioning

confidence: 98%

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Empowering gamma delta T cells with antitumor immunity by dendritic cell-based immunotherapy

Anguille

et al. 2015

OncoImmunology

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These authors equally contributed to the work.Keywords: gd T cell, cancer, DC-mediated gd T cell activation, dendritic cell, immunotherapy Abbreviations: gd, gamma delta; BCG, Bacillus Calmette-Guerin; BrHPP, bromohydrin pyrophosphate; CTL, cytotoxic T lymphocyte; DC, dendritic cell; GM-CSF, granulocyte-macrophage colony-stimulating factor; HIV, human immunodeficiency virus; HMBPP, (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate; iDC, immature DC; IFN, interferon; IL, interleukin; IPP, isopentyl pyrophosphate; mDC, myeloid dendritic cell; MHC, major histocompatibility complex; mo-DC, monocyte-derived dendritic cell; pDC, plasmacytoid dendritic cell; PD, programmed cell death protein; TCR, T-cell receptor; Th, T-helper cell; TLR, toll-like receptor; TNF, tumor necrosis factor; Treg, regulatory T cellGamma delta (gd) T cells are the all-rounders of our immune-system with their major histocompatibility complexunrestricted cytotoxicity, capacity to secrete immunostimulatory cytokines and ability to promote the generation of tumor antigen-specific CD8 C and CD4 C T cell responses. Dendritic cell (DC)-based vaccine therapy has the prospective to harness these unique features of the gd T cells in the fight against cancer. In this review, we will discuss our current knowledge on DC-mediated gd T cell activation and related opportunities for tumor immunologists.

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Section: Discussionmentioning

confidence: 99%

Section: Gd T Cells and Cancer Immunitymentioning

confidence: 98%

Empowering gamma delta T cells with antitumor immunity by dendritic cell-based immunotherapy

Anguille

et al. 2015

OncoImmunology

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“…Recent studies have shown a high frequency of γδ 1 T cells among TILs or circulating peripheral blood mononuclear cells (PBMC) from cancer patients with renal carcinoma tumors, acute leukemia and squamous cell carcinoma of the head and neck (41–44). Furthermore, we demonstrated that high percentages of γδ1 Treg cells with potent suppressive function existed in breast cancer TILs (6).…”

Section: Discussionmentioning

confidence: 99%

Tumor-Infiltrating γδ T Lymphocytes Predict Clinical Outcome in Human Breast Cancer

Zhang

et al. 2012

The Journal of Immunology

197

160

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Understanding and dissecting the role of different subsets of regulatory tumor-infiltrating T lymphocytes (TILs) in the immunopathogenesis of individual cancer is a challenge for anti-tumor immunotherapy. High levels of γδ regulatory T (Treg) cells have been discovered in the breast TILs. However, the clinical relevance of these intra-tumoral γδ T cells is unknown. In this study, γδ T cell populations were analyzed by performing immunohistochemical staining in primary breast cancer tissues from patients with different stages of cancer progression. Retrospective multivariate analyses of the correlations between γδ T cell levels and other prognostic factors and clinical outcomes were completed. We found that γδ T cell infiltration and accumulation in breast tumor sites was a general feature in breast cancer patients. Intra-tumoral γδ T cell numbers were positively correlated with advanced tumor stages, HER2 expression status and high lymph node metastasis, but inversely correlated with relapse-free survival (RFS) and overall survival (OS) of breast cancer patients. Multivariate and univariate analyses of tumor-infiltrating γδ T cells and other prognostic factors further suggested that intra-tumoral γδ T cells were the most significant independent prognostic factor for assessing severity of breast cancer, compared with the other known factors. Intra-tumoral γδ T cells were positively correlated with FoxP3+ cells and CD4+ T cells, but negatively correlated with CD8+ T cells in breast cancer tissues. These findings suggest that intra-tumoral γδ T cells may serve as a valuable and independent prognostic biomarker, as well as a potential therapeutic target for human breast cancer.

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“…Moreover, they have an immunoregulatory function, producing various cytokines, including the T helper (Th)1-associated cytokines tumor necrosis factor (TNF)-α and interferon (IFN)-γ [ 1 ]. γδ T cells are considered to be important players in cancer immune surveillance evidenced by; (a) the increased incidence of tumors in γδ T cell deficient mice [ 2 , 3 ], (b) the overrepresentation of γδ T cells in reactive lymphatic regions associated with neoplasia, including acute myeloid leukemia (AML) [ 4 ], (c) their infiltration into solid tumors [ 5 ], and (d) their potential to kill a variety of tumor cells [ 1 ]. Pointedly, tumor-infiltrating γδ T cells recently emerged as the most significant favorable prognostic immune population across 39 malignancies [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

Interleukin-15 enhances the proliferation, stimulatory phenotype, and antitumor effector functions of human gamma delta T cells

et al. 2016

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BackgroundAdoptive immunotherapy is gaining momentum to fight malignancies, whereby γδ T cells have received recent attention as an alternative cell source as to natural killer cells and αβ T cells. The advent of γδ T cells is largely due to their ability to recognize and target tumor cells using both innate characteristic and T cell receptor (TCR)-mediated mechanisms, their capacity to enhance the generation of antigen-specific T cell responses, and their potential to be used in an autologous or allogeneic setting.MethodsIn this study, we explored the beneficial effect of the immunostimulatory cytokine interleukin (IL)-15 on purified γδ T cells and its use as a stimulatory signal in the ex vivo expansion of γδ T cells for adoptive transfer. The expansion protocol was validated both with immune cells of healthy individuals and acute myeloid leukemia patients.ResultsWe report that the addition of IL-15 to γδ T cell cultures results in a more activated phenotype, a higher proliferative capacity, a more pronounced T helper 1 polarization, and an increased cytotoxic capacity of γδ T cells. Moreover γδ T cell expansion starting with peripheral blood mononuclear cells from healthy individuals and acute myeloid leukemia patients is boosted in the presence of IL-15, whereby the antitumor properties of the γδ T cells are strengthened as well.ConclusionsOur results support the rationale to explore the use of IL-15 in clinical adoptive therapy protocols exploiting γδ T cells.

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Flow cytometric assessment of autologous γδ T cells in patients with acute myeloid leukemia: Potential effector cells for immunotherapy?

Cited by 14 publications

References 73 publications

Empowering gamma delta T cells with antitumor immunity by dendritic cell-based immunotherapy

Empowering gamma delta T cells with antitumor immunity by dendritic cell-based immunotherapy

Tumor-Infiltrating γδ T Lymphocytes Predict Clinical Outcome in Human Breast Cancer

Interleukin-15 enhances the proliferation, stimulatory phenotype, and antitumor effector functions of human gamma delta T cells

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