Modeling the Th17 and Tregs Paradigm: Implications for Cancer Immunotherapy

Corral-Jara, Karla Fabiola; Silva, Gonçalo Rosas da; Fierro, Nora A.; Soumelis, Vassili

doi:10.3389/fcell.2021.675099

Cited by 9 publications

(9 citation statements)

References 131 publications

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“…Another pro-tumor effect of FAs is that FAs catalyzed by ACC1 will fuel the differentiation of Tregs and Th17 ( 105 ). Tregs and Th17 have the synergistic effects in tumor-promoting with IL-6 and TGF-β secreted themselves ( 106 ). SREBP, a family of membrane-bound transcriptional regulators in ER, are mainly involved in FA and cholesterol synthesis.…”

Section: The Lipid Metabolism Of Immune Cells In Tmementioning

confidence: 99%

The role of lipid metabolism in tumor immune microenvironment and potential therapeutic strategies

Wang

et al. 2022

Front. Oncol.

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Aberrant lipid metabolism is nonnegligible for tumor cells to adapt to the tumor microenvironment (TME). It plays a significant role in the amount and function of immune cells, including tumor-associated macrophages, T cells, dendritic cells and marrow-derived suppressor cells. It is well-known that the immune response in TME is suppressed and lipid metabolism is closely involved in this process. Immunotherapy, containing anti-PD1/PDL1 therapy and adoptive T cell therapy, is a crucial clinical cancer therapeutic strategy nowadays, but they display a low-sensibility in certain cancers. In this review, we mainly discussed the importance of lipid metabolism in the formation of immunosuppressive TME, and explored the effectiveness and sensitivity of immunotherapy treatment by regulating the lipid metabolism.

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Section: The Lipid Metabolism Of Immune Cells In Tmementioning

confidence: 99%

The role of lipid metabolism in tumor immune microenvironment and potential therapeutic strategies

Wang

et al. 2022

Front. Oncol.

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“…The tumor immune microenvironment is closely associated with the aggressive development and therapeutic resistance of GBM. GBM cells commonly exhibit immune evasion or even interact with immune cells, thereby triggering malignant progression by secreting cytokines ( Lei and Lee, 2021 ; Corral-Jara et al, 2021 ). LncRNAs were also involved in mediating immune evasion in GBM progression.…”

Section: Significance Of Lncrnas In Gbm Malignant Phenotypesmentioning

confidence: 99%

Evolving Insights Into the Biological Function and Clinical Significance of Long Noncoding RNA in Glioblastoma

Liu

Chen

Wang

et al. 2022

Front. Cell Dev. Biol.

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Glioblastoma (GBM) is one of the most prevalent and aggressive cancers worldwide. The overall survival period of GBM patients is only 15 months even with standard combination therapy. The absence of validated biomarkers for early diagnosis mainly accounts for worse clinical outcomes of GBM patients. Thus, there is an urgent requirement to characterize more biomarkers for the early diagnosis of GBM patients. In addition, the detailed molecular basis during GBM pathogenesis and oncogenesis is not fully understood, highlighting that it is of great significance to elucidate the molecular mechanisms of GBM initiation and development. Recently, accumulated pieces of evidence have revealed the central roles of long noncoding RNAs (lncRNAs) in the tumorigenesis and progression of GBM by binding with DNA, RNA, or protein. Targeting those oncogenic lncRNAs in GBM may be promising to develop more effective therapeutics. Furthermore, a better understanding of the biological function and underlying molecular basis of dysregulated lncRNAs in GBM initiation and development will offer new insights into GBM early diagnosis and develop novel treatments for GBM patients. Herein, this review builds on previous studies to summarize the dysregulated lncRNAs in GBM and their unique biological functions during GBM tumorigenesis and progression. In addition, new insights and challenges of lncRNA-based diagnostic and therapeutic potentials for GBM patients were also introduced.

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“…The role of Tregs and impaired T cell homeostasis has been well characterized in prominent metabolic diseases (from diabetes, cancer and cardio vascular diseases) [99][100][101][102][103] . Subjects presenting such metabolic aberrations have impaired host/microbe driven metabolic pro les that impair T cell function.…”

Section: Increased Frequencies Of Senescent Pd1+ Tcms With Impaired Mitochondrial Function Drive Lower Cd4 Counts In the Senescent Inrsmentioning

confidence: 99%

TGF-β associated senescence and impaired metabolism in central memory CD4 T cells promotes HIV persistence

Sékaly

Ghneim

Sharma

et al. 2021

Preprint

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Current therapeutic interventions to eradicate latent HIV (“reservoir”) and restore immune function in ART-treated HIV infection have yet to show efficacy. To explore mechanisms of HIV persistence, we apply an integrated systems biology approach and identify a distinct group of individuals with poor CD4 T-cell reconstitution (Immunologic non-responders, “INRs”) and high frequencies of cells with inducible HIV. Contrary to the prevailing notion that immune activation drives HIV persistence and immune dysfunction, peripheral blood leukocytes from these subjects have enhanced expression of a network of genes regulated by cellular senescence. In these subjects, increased frequencies of regulatory T cells and expression of the TGF-β signaling cascade are concomitant with the downregulation of cell cycle and metabolism in CD4 central memory T (TCM) cells. These cascades, downstream of TGF-β, lead to the accumulation of PD-1 expressing CD4 TCM and are associated with an increase in frequencies of cells with inducible HIV ex vivo. In vitro validation confirmed that this cellular profile was driven by a β-hydroxybutyrates/bile acid rich metabolic milieu and resulted in TGF-β associated latency establishment. Our findings identify targets for PD-1 or TGF-β specific interventions that can overcome cellular senescence; these therapeutic approaches have shown safety and efficacy in cancer, and may prove to be crucial for HIV eradication.

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Modeling the Th17 and Tregs Paradigm: Implications for Cancer Immunotherapy

Cited by 9 publications

References 131 publications

The role of lipid metabolism in tumor immune microenvironment and potential therapeutic strategies

The role of lipid metabolism in tumor immune microenvironment and potential therapeutic strategies

Evolving Insights Into the Biological Function and Clinical Significance of Long Noncoding RNA in Glioblastoma

TGF-β associated senescence and impaired metabolism in central memory CD4 T cells promotes HIV persistence

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