Prognostic Values of Transforming Growth Factor-Beta Subtypes in Ovarian Cancer

Zhou, Jingyang; Jiang, Wenxiao; Huang, Wenbin; Zhu, Xueqiong

doi:10.1155/2020/2170606

Cited by 7 publications

(4 citation statements)

References 31 publications

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“… 62 The Tregs then produce more TGF-β, further increasing immunosuppression within the tumor, which impedes CAR T-cell function. High levels of TGF-β within the TME have been shown to correspond to poor prognosis in patients, 63–65 demonstrating that reducing TGF-β mediated immunosuppression in solid tumors may be key to enhancing CAR T-cell efficacy and clinical outcome.…”

Section: Armored Car T-cellsmentioning

confidence: 99%

Armored CAR T-Cells: The Next Chapter in T-Cell Cancer Immunotherapy

Hawkins¹,

D'Souza²,

Klampatsa³

2021

BTT

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Chimeric antigen receptor (CAR) T-cell therapy engineers T-cells to express a synthetic receptor which redirects effector function to the tumor, to improve efficacy and reduce toxicities associated with conventional treatments, such as radiotherapy and chemotherapy. This approach has proved effective in treating hematological malignancies; however, the same effects have not been observed in solid tumors. The immunosuppressive tumor microenvironment (TME) creates a significant barrier to solid tumor efficacy and reduces the anti-cancer activity of endogenous tumor-resident immune cells, enabling cancer progression. In recent years, researchers have attempted to enhance CAR T-cell function in the TME by engineering the cells to express various proteins alongside the CAR. Examples of this engineering include inducing CAR T-cells to secrete cytokines or express cytokine receptors to modulate the cytokine milieu of the TME. Alternatively, the CAR T-cell may secrete antibody-like proteins to target a range of tumor antigens. Collectively, these methods are termed armored CAR T-cell therapy, and in this review, we will discuss the range of armored CAR T-cell approaches which have been investigated to date.

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Section: Armored Car T-cellsmentioning

confidence: 99%

Armored CAR T-Cells: The Next Chapter in T-Cell Cancer Immunotherapy

Hawkins¹,

D'Souza²,

Klampatsa³

2021

BTT

View full text Add to dashboard Cite

show abstract

“…Such studies have revealed lack of a robust correlation between TGFβ1 expression and survival outcomes in women with ovarian cancer. However most notably, increased TGFβ2 and TGFβ3 mRNA expression were associated with poorer prognosis based on worse progression-free survival (PFS) and reduced overall survival (OS) [ 145 ]. While the utility of the TGFβ ligand expression as a biomarker continues to be debated, there is significant evidence that all isoforms are produced albeit at different locations and to different degrees.…”

Section: Tgfβ Family In Ovarian and Related Cancersmentioning

confidence: 99%

TGFβ signaling networks in ovarian cancer progression and plasticity

Asha

Shonibare

Monavarian

et al. 2021

Clin Exp Metastasis

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Epithelial ovarian cancer (EOC) is a leading cause of cancer-related death in women. Late-stage diagnosis with significant tumor burden, accompanied by recurrence and chemotherapy resistance, contributes to this poor prognosis. These morbidities are known to be tied to events associated with epithelial-mesenchymal transition (EMT) in cancer. During EMT, localized tumor cells alter their polarity, cell–cell junctions, cell–matrix interactions, acquire motility and invasiveness and an exaggerated potential for metastatic spread. Key triggers for EMT include the Transforming Growth Factor-β (TGFβ) family of growth factors which are actively produced by a wide array of cell types within a specific tumor and metastatic environment. Although TGFβ can act as either a tumor suppressor or promoter in cancer, TGFβ exhibits its pro-tumorigenic functions at least in part via EMT. TGFβ regulates EMT both at the transcriptional and post-transcriptional levels as outlined here. Despite recent advances in TGFβ based therapeutics, limited progress has been seen for ovarian cancers that are in much need of new therapeutic strategies. Here, we summarize and discuss several recent insights into the underlying signaling mechanisms of the TGFβ isoforms in EMT in the unique metastatic environment of EOCs and the current therapeutic interventions that may be relevant.

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“…transformation of fibroblasts and regulate cell proliferation and apoptosis (56). The high expression of TGF-β3 is associated with poor prognosis of high-grade serous carcinoma, and it is a potential indicator for the evaluation of ovarian cancer prognosis (57). Recent studies have reported that in ovarian cancer stem cells, inhibition of TGF-β/SMAD pathway activation can further inhibit EMT (58)(59)(60).…”

Section: Cell Signaling and Exosome-mediated Tumor Immune Microenviromentioning

confidence: 99%

Role of exosomes in the immune microenvironment of ovarian cancer (Review)

et al. 2021

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Exosomes are excretory vesicles that can deliver a variety of bioactive cargo molecules to the extracellular environment. Accumulating evidence demonstrates exosome participation in intercellular communication, immune response, inflammatory response and they even play an essential role in affecting the tumor immune microenvironment. The role of exosomes in the immune microenvironment of ovarian cancer is mainly divided into suppression and stimulation. On one hand exosomes can stimulate the innate and adaptive immune systems by activating dendritic cells (DCs), natural killer cells and T cells, allowing these immune cells exert an antitumorigenic effect. On the other hand, ovarian cancer-derived exosomes initiate cross-talk with immunosuppressive effector cells, which subsequently cause immune evasion; one of the hallmarks of cancer. Exosomes induce the polarization of macrophages in M2 phenotype and induce apoptosis of lymphocytes and DCs. Exosomes further activate additional immunosuppressive effector cells (myeloid-derived suppressor cells and regulatory T cells) that induce fibroblasts to differentiate into cancer-associated fibroblasts. Exosomes also induce the tumorigenicity of mesenchymal stem cells to exert additional immune suppression. Furthermore, besides mediating the intercellular communication, exosomes carry microRNAs (miRNAs), proteins and lipids to the tumor microenvironment, which collectively promotes ovarian cancer cells to proliferate, invade and tumors to metastasize. Studying proteins, lipids and miRNAs carried by exosomes could potentially be used as an early diagnostic marker of ovarian cancer for designing treatment strategies.

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Prognostic Values of Transforming Growth Factor-Beta Subtypes in Ovarian Cancer

Cited by 7 publications

References 31 publications

Armored CAR T-Cells: The Next Chapter in T-Cell Cancer Immunotherapy

Armored CAR T-Cells: The Next Chapter in T-Cell Cancer Immunotherapy

TGFβ signaling networks in ovarian cancer progression and plasticity

Role of exosomes in the immune microenvironment of ovarian cancer (Review)

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