scholarly journals Therapeutic targeting of TGF-β in cancer: hacking a master switch of immune suppression

2021 ◽  
Vol 135 (1) ◽  
pp. 35-52
Author(s):  
Jitske van den Bulk ◽  
Noel F.C.C. de Miranda ◽  
Peter ten Dijke
Keyword(s):  
T Cell ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Tumour Microenvironment ◽  
Checkpoint Blockade ◽  
Host Immune System ◽  
Therapeutic Targeting ◽  
Invasion And Migration ◽  
And Migration ◽  
Multifunctional Cytokine

Abstract Cancers may escape elimination by the host immune system by rewiring the tumour microenvironment towards an immune suppressive state. Transforming growth factor-β (TGF-β) is a secreted multifunctional cytokine that strongly regulates the activity of immune cells while, in parallel, can promote malignant features such as cancer cell invasion and migration, angiogenesis, and the emergence of cancer-associated fibroblasts. TGF-β is abundantly expressed in cancers and, most often, its abundance associated with poor clinical outcomes. Immunotherapeutic strategies, particularly T cell checkpoint blockade therapies, so far, only produce clinical benefit in a minority of cancer patients. The inhibition of TGF-β activity is a promising approach to increase the efficacy of T cell checkpoint blockade therapies. In this review, we briefly outline the immunoregulatory functions of TGF-β in physiological and malignant contexts. We then deliberate on how the therapeutic targeting of TGF-β may lead to a broadened applicability and success of state-of-the-art immunotherapies.

scholarly journals LncRNA SNHG16 promotes pulmonary fibrosis by targeting miR-455-3p to regulate the Notch2 pathway

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Panpan Liu ◽  
Lei Zhao ◽  
Yuxia Gu ◽  
Meilan Zhang ◽  
Hongchang Gao ◽  
...  
Keyword(s):  
Pulmonary Fibrosis ◽  
Lung Fibrosis ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Interstitial Lung Diseases ◽  
Luciferase Reporter ◽  
Qrt Pcr ◽  
Rna Immunoprecipitation ◽  
And Migration

Abstract Background Idiopathic pulmonary fibrosis (IPF) is the most common interstitial lung diseases with a poor prognosis. Long non-coding RNAs (lncRNAs) have been reported to be involved in IPF in several studies. However, the role of lncRNA SNHG16 in IPF is largely unknown. Methods Firstly, experimental pulmonary fibrosis model was established by using bleomycin (BML). Histology and Western blotting assays were used to determine the different stages of fibrosis and expression of several fibrosis biomarkers. The expression of SNHG16 was detected by quantitative real-time polymerase chain reaction (qRT‐PCR). EdU staining and wound-healing assay were utilized to analyze proliferation and migration of lung fibroblast cells. Molecular mechanism of SNHG16 was explored by bioinformatics, dual-luciferase reporter assay, RNA immunoprecipitation assay (RIP), and qRT-PCR. Results The expression of SNHG16 was significantly up-regulated in bleomycin-(BLM) induced lung fibrosis and transforming growth factor-β (TGF-β)-induced fibroblast. Knockdown of SNHG16 could attenuate fibrogenesis. Mechanistically, SNHG16 was able to bind and regulate the expression of miR-455-3p. Moreover, SNHG16 also regulated the expression of Notch2 by targeting miR-455-3p. Finally, SNHG16 could promote fibrogenesis by regulating the expression of Notch2. Conclusion Taken together, our study demonstrated that SNHG16 promoted pulmonary fibrosis by targeting miR-455-3p to regulate the Notch2 pathway. These findings might provide a novel insight into pathologic process of lung fibrosis and may provide prevention strategies in the future.

scholarly journals Amygdalin promotes the activity of T cells to suppress the progression of HBV-related hepatocellular carcinoma via the JAK2/STAT3 signaling pathway

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Ruoyu Wang ◽  
Dong Zhang ◽  
Kewei Sun ◽  
Jianping Peng ◽  
Wenfang Zhu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Proliferation ◽  
T Cells ◽  
T Cell ◽  
Cell Viability ◽  
Caspase 3 ◽  
Invasion And Migration ◽  
Ifn Γ ◽  
And Migration ◽  
Cellular Immune

Abstract Background Hepatitis B virus (HBV) infection is a high-risk factor of hepatocellular carcinoma (HCC). Cellular immune responses are essential for HCC development, and the CD4+ and CD8+ T subtypes are identified as the primary anti-tumor immune cells. In the study, we investigated the effect and mechanism of amygdalin in the cellular immune response in HBV-related HCC and HCC progression. Methods The cell proliferation was examined by MTT analysis. Cells metastasis ability was detected by Invasion and migration assays. Quantification of apoptotic cells was performed with Flow cytometer assay. The protein levels of p-STAT3, STAT3, p-JAK2, JAK2, caspase-3, cleaved caspase-3 were detected by performing immunoblotting assays. Results We demonstrate that amygdalin treatment could rescue the HBV-T cell viability and IFN-γ and TNF-αproduction. In HBV-T cells, the MFI levels of CD8+ are lower than that in NC-T cells. Moreover, the phosphorylation levels of STAT3 and JAK2 are higher in HBV-T cells, compared to those in NC-T cells, and then reduced by amygdalin treatment. Co-culture with HBV-T cells could reduce IFN-γ and TNF-α, production while increase IL-6 and IL-10 production in HepG2.2.15 cells; these alterations could be partially reversed by amygdalin pretreatment. Finally, co-culture with HBV-T cells significantly promoted the cell viability, inhibited the apoptosis, and promoted the migration of HepG2.2.15 cells, and these alterations could be partially reversed by amygdalin treatment. Conclusion Our findings provide a rationale for further studies on the functions and mechanism of amygdalin inhibiting HBV-related HCC cell proliferation, invasion, and migration via T cell-mediated tumor immunity.

scholarly journals Cell-Intrinsic Transforming Growth Factor-β Signaling Mediates Virus-Specific CD8+ T Cell Deletion and Viral Persistence In Vivo

Immunity ◽  
2009 ◽  
Vol 31 (1) ◽  
pp. 145-157 ◽  
Author(s):  
Roberto Tinoco ◽  
Victor Alcalde ◽  
Yating Yang ◽  
Karsten Sauer ◽  
Elina I. Zuniga
Keyword(s):  
T Cell ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Viral Persistence ◽  
Transforming Growth Factor Β ◽  
Cd8 T Cell ◽  
Cell Deletion

Transforming growth factor-β in T cell tolerance

2007 ◽  
pp. 3-6
Author(s):  
M. O. Li ◽  
Y. Laouar ◽  
Y. Peng ◽  
L. Gorelik ◽  
R. A. Flavell
Keyword(s):  
T Cell ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
T Cell Tolerance ◽  
Cell Tolerance

scholarly journals Latency-Associated Peptide of Transforming Growth Factor β Enhances Mycobacteriocidal Immunity in the Lung duringMycobacterium bovis BCG Infection in C57BL/6 Mice

2000 ◽  
Vol 68 (11) ◽  
pp. 6505-6508 ◽  
Author(s):  
K. A. Wilkinson ◽  
T. D. Martin ◽  
S. M. Reba ◽  
H. Aung ◽  
R. W. Redline ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
T Cell ◽  
Growth Factor ◽  
Mrna Expression ◽  
Mycobacterium Bovis ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Gamma Interferon ◽  
T Cell Proliferation

ABSTRACT Latency-associated peptide of transforming growth factor β (TGF-β) (LAP) was used to determine whether in vivo modulation of TGF-β bioactivity enhanced pulmonary immunity to Mycobacterium bovis BCG infection in C57BL/6 mice. LAP decreased BCG growth in the lung and enhanced antigen-specific T-cell proliferation and gamma interferon mRNA expression. Thus, susceptibility of the lung to primary BCG infection may be partially mediated by the immunosuppressive effects of TGF-β.

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