Tripartite immune cell co‐operation in the Bacillus Calmette Guérin‐induced activation of γδ T cells

Fowler, Daniel; Copier, John; Dalgleish, Angus; Bodman‐Smith, Mark

doi:10.1038/icb.2013.30

Cited by 6 publications

(13 citation statements)

References 46 publications

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“…In another study, it was reported that Vδ2 cells are indirectly activated by BCG and IL-12p70 secreted by DCs. IL-12p70 production by DC is modulated by Toll like receptor 2/4 ligands from BCG and IFN-γ secreted by memory CD4 T cells (141). This study portrayed the complex interplay between cells of the innate and adaptive immune response in contributing to immunosurveillance against pathogenic infections.…”

Section: Tlrs Modulate Crosstalk Between γδ T and Dendritic Cellsmentioning

confidence: 99%

Insights into the Relationship between Toll Like Receptors and Gamma Delta T Cell Responses

2014

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The tumor microenvironment is an important aspect of cancer biology that contributes to tumor initiation, tumor progression and responses to therapy. The composition and characteristics of the tumor microenvironment vary widely and are important in determining the anti-tumor immune response. Successful immunization requires activation of both innate and adaptive immunity. Generally, immune system is compromised in patients with cancer due to immune suppression, loss of tumor antigen expression and dysfunction of antigen presenting cells (APC). Thus, therapeutic immunization leading to cancer regression remains a significant challenge. Certain cells of the immune system, including dendritic cells (DCs) and gamma delta (γδ) T cells are capable of driving potent anti-tumor responses. The property of MHC-unrestricted cytotoxicity, high potential of cytokine release, tissue tropism and early activation in infections and malignant disease makes γδ T cells as an emerging candidate for immunotherapy. Various strategies are being developed to enhance anti-tumor immune responses of γδ T cells and DCs one of them is the use of novel adjuvants like toll like receptors (TLR) agonists, which enhance γδ T cell function directly or through DC activation, which has ability to prime γδ T cells. TLR agonists are being used clinically either alone or in combination with tumor antigens and has shown initial success in both enhancing immune responses and eliciting anti-tumor activity. TLR activated γδ T cells and DCs nurture each other’s activation. This provides a potent base for first line of defense and manipulation of the adaptive response against pathogens and cancer. The available data provides a strong rationale for initiating combinatorial therapy for the treatment of diseases and this review will summarize the application of adjuvants (TLRs) for boosting immune response of γδ T cells to treat cancer and infectious diseases and their use in combinatorial therapy.

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Section: Tlrs Modulate Crosstalk Between γδ T and Dendritic Cellsmentioning

confidence: 99%

Insights into the Relationship between Toll Like Receptors and Gamma Delta T Cell Responses

2014

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“…9 The importance of IL-12, along with IL-1b and TNF-a, secretion by BCG-DCs has been demonstrated by the increased production of IFN-g, granzyme B, and the augmented cytotoxicity of Vg9d2 T cells against Daudi cells, pertaining to the IL-12-blocked conditions. 71,72 The IL-12 secretion by BCG blood DCs relies on IFN-g production of memory CD4 C T cells, reveling a complex biology between cells of the innate and adaptive immune system. 71 IL-12 however does not seems to have an indisputable positive effect.…”

Section: Mechanisms Behind Dc-mediated Gd T Cell Activationmentioning

confidence: 99%

“…71,72 The IL-12 secretion by BCG blood DCs relies on IFN-g production of memory CD4 C T cells, reveling a complex biology between cells of the innate and adaptive immune system. 71 IL-12 however does not seems to have an indisputable positive effect. IL-12 secreting DCs, in contrast to DCs that are not enabled for IL-12 secretion, give rise to immune suppression by gd T cells.…”

Section: Mechanisms Behind Dc-mediated Gd T Cell Activationmentioning

confidence: 99%

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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“…54 Such approaches could be combined with better ways of priming the anti-tumour programme in peripheral cd T cells that do not elicit targeting of self; for instance, we have previously shown that bacillus Calmette-Gu erin can indirectly activate cd T cells without inducing cytotoxicity against immune cells. 31,55 In conclusion, our data provide a novel insight into the complex immunological interaction between cd T cells and monocytes, and suggest that ZA-induced activation of cd T cells is a double-edged sword that can result in inappropriate targeting of self and reduced tumour-homing. These previously unexplored effects of ZA could prove to be useful in the design of future clinical trials using this drug.…”

Section: Discussionmentioning

confidence: 71%

“…Delivering ZA directly to the tumour mass would also circumvent the rapid binding of ZA to the hydroxyapatite crystals of the bone matrix that may limit its potential to reach tumours that are not closely associated with blood or bone . Such approaches could be combined with better ways of priming the anti‐tumour programme in peripheral γδ T cells that do not elicit targeting of self; for instance, we have previously shown that bacillus Calmette–Guérin can indirectly activate γδ T cells without inducing cytotoxicity against immune cells …”

Section: Discussionmentioning

confidence: 99%

Zoledronic acid causes γδ T cells to target monocytes and down‐modulate inflammatory homing

et al. 2014

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SummaryZoledronic acid (ZA) is a potential immunotherapy for cancer because it can induce potent cd T-cell-mediated anti-tumour responses. Clinical trials are testing the efficacy of intravenous ZA in cancer patients; however, the effects of systemic ZA on the activation and migration of peripheral cd T cells remain poorly understood. We found that cd T cells within ZAtreated peripheral blood mononuclear cells were degranulating, as shown by up-regulated expression of CD107a/b. Degranulation was monocyte dependent because CD107a/b expression was markedly reduced in the absence of CD14 + cells. Consistent with monocyte-induced degranulation,we observed cd T-cell-dependent induction of monocyte apoptosis, as shown by phosphatidylserine expression on monocytes and decreased percentages of monocytes in culture. Despite the prevailing paradigm that ZA promotes tumour homing in cd T cells, we observed down-modulation of their tumour homing capacity, as shown by decreased expression of the inflammatory chemokine receptors CCR5 and CXCR3, and reduced migration towards the inflammatory chemokine CCL5. Taken together our data suggest that ZA causes cd T cells to target monocytes and downmodulate the migratory programme required for inflammatory homing. This study provides novel insight into how cd T cells interact with monocytes and the possible implications of systemic use of ZA in cancer.

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Tripartite immune cell co‐operation in the Bacillus Calmette Guérin‐induced activation of γδ T cells

Cited by 6 publications

References 46 publications

Insights into the Relationship between Toll Like Receptors and Gamma Delta T Cell Responses

Insights into the Relationship between Toll Like Receptors and Gamma Delta T Cell Responses

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

Zoledronic acid causes γδ T cells to target monocytes and down‐modulate inflammatory homing

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