NK Cell Function Regulation by TGF-β-Induced Epigenetic Mechanisms

Regis, Stefano; Dondero, Alessandra; Caliendo, Fabio; Bottino, Cristina; Castriconi, Roberta

doi:10.3389/fimmu.2020.00311

Cited by 65 publications

(49 citation statements)

References 57 publications

(74 reference statements)

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“…Multiple studies have evaluated the role of TGF-β signaling pathway in different malignancies and disorders. It is not possible to comprehensively discuss the role of TGF-β signaling in diseases in this article (limitation of space) and we cite some of the great reviews for further information ( Fionda et al, 2020 ; Munoz et al, 2020 ; Regis et al, 2020 ). However, we briefly describe the role of TGF-β signaling pathway in pathological events to pave the road for discussing the relationship between curcumin and TGF-β in different diseases.…”

Section: Transforming Growth Factor-beta Signaling Pathway: From Basimentioning

confidence: 99%

Toward Regulatory Effects of Curcumin on Transforming Growth Factor-Beta Across Different Diseases: A Review

et al. 2020

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Immune response, proliferation, migration and angiogenesis are juts a few of cellular events that are regulated by transforming growth factor-β (TGF-β) in cells. A number of studies have documented that TGF-β undergoes abnormal expression in different diseases, e.g., diabetes, cancer, fibrosis, asthma, arthritis, among others. This has led to great fascination into this signaling pathway and developing agents with modulatory impact on TGF-β. Curcumin, a natural-based compound, is obtained from rhizome and roots of turmeric plant. It has a number of pharmacological activities including antioxidant, anti-inflammatory, anti-tumor, anti-diabetes and so on. Noteworthy, it has been demonstrated that curcumin affects different molecular signaling pathways such as Wnt/β-catenin, Nrf2, AMPK, mitogen-activated protein kinase and so on. In the present review, we evaluate the potential of curcumin in regulation of TGF-β signaling pathway to corelate it with therapeutic impacts of curcumin. By modulation of TGF-β (both upregulation and down-regulation), curcumin ameliorates fibrosis, neurological disorders, liver disease, diabetes and asthma. Besides, curcumin targets TGF-β signaling pathway which is capable of suppressing proliferation of tumor cells and invading cancer cells.

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Section: Transforming Growth Factor-beta Signaling Pathway: From Basimentioning

confidence: 99%

Toward Regulatory Effects of Curcumin on Transforming Growth Factor-Beta Across Different Diseases: A Review

et al. 2020

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“…Indeed, in the absence of TGF‐β signaling, SMAD4 can associate to JUNB to positively regulate GrzB transcription in NK cells 172 . TGF‐β1 also affects NK cell function by acting on various miRNA targeting different effector molecules and receptors 174 . For example, TGF‐β1 (and IL‐10) induces expression of the STAT1/perforin inhibitor miR146a (see above) 39 .…”

Section: Tumor Escape Strategiesmentioning

confidence: 99%

“…The expression of NK receptor ligands can also be regulated at post‐transcriptional level, through the action of several miRNAs 174,283,284 . In particular, tumor cells can overexpress miRNAs involved in the down‐regulation of NKG2D ligands.…”

Section: Tumor Escape Strategiesmentioning

confidence: 99%

“…281,282 The expression of NK receptor ligands can also be regulated at posttranscriptional level, through the action of several miRNAs. 174,283,284 In particular, tumor cells can overexpress miRNAs involved in the down-regulation of NKG2D ligands. For instance, MICA is targeted by different miRNAs, including miR-183 (up-regulated by TGF-), miR-20a, miR-146b-5p, and miR-25/93/106b.…”

Section: Modulation Of Cytotoxic Effector Moleculesmentioning

confidence: 99%

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Escape of tumor cells from the NK cell cytotoxic activity

Cantoni

Wurzer

Thomas

et al. 2020

Journal of Leukocyte Biology

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In recent years, NK cells, initially identified as potent cytotoxic effector cells, have revealed an unexpected complexity, both at phenotypic and functional levels. The discovery of different NK cell subsets, characterized by distinct gene expression and phenotypes, was combined with the characterization of the diverse functions NK cells can exert, not only as circulating cells, but also as cells localized or recruited in lymphoid organs and in multiple tissues. Besides the elimination of tumor and virus-infected cells, these functions include the production of cytokines and chemokines, the regulation of innate and adaptive immune cells, the influence on tissue homeostasis. In addition, NK cells display a remarkable functional plasticity, being able to adapt to the environment and to develop a kind of memory. Nevertheless, the powerful cytotoxic activity of NK cells remains one of their most relevant properties, particularly in the antitumor response. In this review, the process of tumor cell recognition and killing mediated by NK cells, starting from the generation of cytolytic granules and recognition of target cell, to the establishment of the NK cell immunological synapse, the release of cytotoxic molecules, and consequent tumor cell death is described. Next, the review focuses on the heterogeneous mechanisms, either intrinsic to tumors or induced by the tumor microenvironment, by which cancer cells can escape the NK cell-mediated attack.

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“…Finally, TGF-β signaling has been found to inhibit the development, differentiation, and activation of cytolytic natural killer (NK) cells [14,27,28]. Several studies have elucidated the distinct mechanisms of TGF-β-mediated NK cell suppression, including alteration of the epigenetic makeup of these cells and upregulation of the mTOR signaling axis [29,30]. TGF-β also suppresses the secretion of interferon γ (IFNγ) by NK cells in a SMAD3-dependent manner, which is essential for tumor suppression by CD4 + TH1 cells [31].…”

Section: Introductionmentioning

confidence: 99%

TGF-β Mediated Immune Evasion in Cancer—Spotlight on Cancer-Associated Fibroblasts

Ghahremanifard

Chanda

Bonni

et al. 2020

Cancers

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Various components of the tumor microenvironment (TME) play a critical role in promoting tumorigenesis, progression, and metastasis. One of the primary functions of the TME is to stimulate an immunosuppressive environment around the tumor through multiple mechanisms including the activation of the transforming growth factor-beta (TGF-β) signaling pathway. Cancer-associated fibroblasts (CAFs) are key cells in the TME that regulate the secretion of extracellular matrix (ECM) components under the influence of TGF-β. Recent reports from our group and others have described an ECM-related and CAF-associated novel gene signature that can predict resistance to immune checkpoint blockade (ICB). Importantly, studies have begun to test whether targeting some of these CAF-associated components can be used as a combinatorial approach with ICB. This perspective summarizes recent advances in our understanding of CAF and TGF-β-regulated immunosuppressive mechanisms and ways to target such signaling in cancer.

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NK Cell Function Regulation by TGF-β-Induced Epigenetic Mechanisms

Cited by 65 publications

References 57 publications

Toward Regulatory Effects of Curcumin on Transforming Growth Factor-Beta Across Different Diseases: A Review

Toward Regulatory Effects of Curcumin on Transforming Growth Factor-Beta Across Different Diseases: A Review

Escape of tumor cells from the NK cell cytotoxic activity

TGF-β Mediated Immune Evasion in Cancer—Spotlight on Cancer-Associated Fibroblasts

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