The role of Foxp3 and Tbet co-expressing Treg cells in lung carcinoma

Kachler, Katerina; Holzinger, Corinna; Trufa, Denis I.; Sı̂rbu, Horia; Finotto, Susetta

doi:10.1080/2162402x.2018.1456612

Cited by 31 publications

(31 citation statements)

References 48 publications

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“…9,10 However, the type of TI-Tregs may vary in different cancers and patients, as Th1-like Tregs, defined by the expression of T-bet, made up 40% of Foxp3 + cells in a murine model of lung carcinoma, and between 2% and 10% of Tregs from human nonsmall cell lung carcinomas. 42 CXCR3, the Th1-defining chemokine receptor, was the most prevalent chemokine receptor on tumour-infiltrating FOXP3 + Treg in human ovarian cancers. 43 Because Th1-like TI-Tregs may best inhibit Th1 effector T-cell responses that are associated with cytotoxic CD8 + T-cells and IFN-c production, selectively eliminating these Tregs may have the greatest effect on potentiating the most effective type of anti-tumour Tcell responses.…”

Section: Chemokine Receptorsmentioning

confidence: 97%

“…CCR8, another chemokine receptor associated with Th2 cells, may prove to be a superior target, as it was found highly expressed on TI‐Tregs in multiple solid tumours, but in a more restricted fashion than CCR4 . However, the type of TI‐Tregs may vary in different cancers and patients, as Th1‐like Tregs, defined by the expression of T‐bet, made up 40% of Foxp3 + cells in a murine model of lung carcinoma, and between 2% and 10% of Tregs from human non‐small cell lung carcinomas . CXCR3, the Th1‐defining chemokine receptor, was the most prevalent chemokine receptor on tumour‐infiltrating FOXP3 + Treg in human ovarian cancers .…”

Section: Activation and Differentiation Of Ti‐tregsmentioning

confidence: 99%

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Treg programming and therapeutic reprogramming in cancer

Ayala

DuPage

2019

Immunology

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Summary Overcoming the immunosuppressive tumour microenvironment is the major challenge impeding cancer immunotherapy today. Regulatory T‐cells (Tregs) are prevalent in nearly all cancers and, as immunosuppressive regulators of immune responses, they are the principal opponents of cancer immunotherapy. However, disabling Tregs systemically causes severe autoimmune toxicity, hastening the need for more selective methods to target intratumoural Tregs. In this review, we discuss a burgeoning new modality to specifically target tumour‐infiltrating Tregs (TI‐Tregs) by reprogramming their functionality from immunosuppressive to immune stimulatory within tumours. As the basis for therapeutic selectivity of TI‐Tregs, we will focus on the defining features of Tregs within cancer: their highly activated state controlled by the engagement of key surface receptors, their distinct metabolic programme, and their unique transcriptional programme. By identifying proteins and pathways that distinguish TI‐Tregs from other Tregs in the body, as well as from the beneficial antitumour effector T‐cells within tumours, we highlight mechanisms to selectively reprogramme TI‐Tregs for the treatment of cancer.

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Section: Chemokine Receptorsmentioning

confidence: 97%

Section: Activation and Differentiation Of Ti‐tregsmentioning

confidence: 99%

Treg programming and therapeutic reprogramming in cancer

Ayala

DuPage

2019

Immunology

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“…Tumour‐infiltrating Treg cells have been widely reported to up‐regulate T helper lineage transcription factors, especially T‐bet, and in some cases GATA‐3 . Both T‐bet‐expressing and GATA‐3‐expressing Treg cells were shown to have enhanced suppression of anti‐tumour CD8 + T cells, without up‐regulating inflammatory cytokines characteristic of their Foxp3 − counterparts.…”

Section: Pi3kδ In Cytokine‐driven Adaptation In Tumour Treg Cellsmentioning

confidence: 99%

“…127,128 Tumour-infiltrating Treg cells have been widely reported to up-regulate T helper lineage transcription factors, especially T-bet, and in some cases GATA-3. [129][130][131] Both T-bet-expressing and GATA-3-expressing Treg cells were shown to have enhanced suppression of anti-tumour CD8 + T cells, without up-regulating inflammatory cytokines characteristic of their Foxp3 À counterparts. Strikingly, Treg cells have been reported to rely on granzyme expression in mediating tumour immunosuppression 132,133 but not in the control of graft-versus-host disease, 134 and it is plausible that an adaptive Th1-like transcriptional programme driven by the expression of T-bet is required for the manifestation of these context-specific suppressive features.…”

Section: Pi3kd In Cytokine-driven Adaptation In Tumour Treg Cellsmentioning

confidence: 99%

Phosphoinositide 3‐kinase δ is a regulatory T‐cell target in cancer immunotherapy

Lim

Okkenhaug

2019

Immunology

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Summary Tumour infiltration by regulatory T (Treg) cells contributes to suppression of the anti‐tumour immune response, which limits the efficacy of immune‐mediated cancer therapies. The phosphoinositide 3‐kinase (PI3K) pathway has key roles in mediating the function of many immune cell subsets, including Treg cells. Treg function is context‐dependent and depends on input from different cell surface receptors, many of which can activate the PI3K pathway. In this review, we explore how PI3Kδ contributes to signalling through several major immune cell receptors, including the T‐cell receptor and co‐stimulatory receptors such as CD28 and ICOS, but is antagonized by the immune checkpoint receptors CTLA‐4 and PD‐1. Understanding how PI3Kδ inhibition affects Treg signalling events will help to inform how best to use PI3Kδ inhibitors in clinical cancer treatment.

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“…Recent studies demonstrated that CD4 + T cells expressing both, T-bet and FoxP3, exert regulatory rather than pro-inflammatory functions. T-bet is required for the expansion of these immunosuppressive cells to limit Th1-mediated immune responses [51,52]. We hypothesized this subset might be involved in pathogen-specific loss of host resistance.…”

Section: Discussionmentioning

confidence: 99%

7-oxo-DHEA enhances impaired M. tuberculosis-specific T cell responses during HIV-TB coinfection

et al. 2020

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Background: Mycobacterium tuberculosis (Mtb) is the causative agent of tuberculosis (TB), affecting approximately one third of the world's population. Development of an adequate immune response will determine disease progression or progress to chronic infection. Risk of developing TB among human immunodeficiency virus (HIV)-coinfected patients (HIV-TB) is 20-30 times higher than those without HIV infection, and a synergistic interplay between these two pathogens accelerates the decline in immunological functions. TB treatment in HIV-TB coinfected persons is challenging and it has a prolonged duration, mainly due to the immune system failure to provide an adequate support for the therapy. Therefore, we aimed to study the role of the hormone 7-oxo-dehydroepiandrosterone (7-OD) as a modulator of anti-tuberculosis immune responses in the context of HIV-TB coinfection. Methods: A cross-sectional study was conducted among HIV-TB patients and healthy donors (HD). We characterized the ex vivo phenotype of CD4 + T cells and also evaluated in vitro antigen-specific responses by Mtb stimulation of peripheral blood mononuclear cells (PBMCs) in the presence or absence of 7-OD. We assessed lymphoproliferative activity, cytokine production and master transcription factor profiles. Results:Our results show that HIV-TB patients were not able to generate successful anti-tubercular responses in vitro compared to HD, as reduced IFN-γ/IL-10 and IFN-γ/IL-17A ratios were observed. Interestingly, treatment with 7-OD enhanced Th1 responses by increasing Mtb-induced proliferation and the production of IFN-γ and TNF-α over IL-10 levels. Additionally, in vitro Mtb stimulation augmented the frequency of cells with a regulatory phenotype, while 7-OD reduced the proportion of these subsets and induced an increase in CD4 + T-bet+ (Th1) subpopulation, which is associated with clinical data linked to an improved disease outcome. Conclusions:We conclude that 7-OD modifies the cytokine balance and the phenotype of CD4 + T cells towards a more favorable profile for mycobacteria control. These results provide new data to delineate novel treatment approaches as co-adjuvant for the treatment of TB.

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The role of Foxp3 and Tbet co-expressing Treg cells in lung carcinoma

Cited by 31 publications

References 48 publications

Treg programming and therapeutic reprogramming in cancer

Treg programming and therapeutic reprogramming in cancer

Phosphoinositide 3‐kinase δ is a regulatory T‐cell target in cancer immunotherapy

7-oxo-DHEA enhances impaired M. tuberculosis-specific T cell responses during HIV-TB coinfection

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