Small extracellular vesicle TGF-β in cancer progression and immune evasion

Hosseini-Ghatar, Reza; Hosseinzadeh, Nima; Asef-Kabiri, Leila; Akbari, Atieh; Ghezelbash, Behrooz; Sarvnaz, Hamzeh; Akbari, Mohammad Esmaeil

doi:10.1038/s41417-023-00638-7

Cited by 6 publications

(4 citation statements)

References 128 publications

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“…Recent studies demonstrate that the secretion of TGF-β in small extracellular vesicles (sEV-TGF-β) contributes to tumor growth, development, and metastasis. Moreover, sEV-TGF-β is also closely related to immune evasion [199]. Interestingly, in non-small-cell lung cancer, the expression of extracellular vesicle (EV) TGF-β was associated with the prediction of efficacy of ICIs and shorter survival, which resulted in a higher accuracy than the existing circulating TGF-β and tissue PD-L1 in patients who are treated with ICIs, suggesting EV TGF-β as a latent predictive biomarker in immunotherapies involving dual TGF-β and PD-L1 blockade [200].…”

Section: Discussion and Future Perspectivementioning

confidence: 99%

The Role of the Transforming Growth Factor-β Signaling Pathway in Gastrointestinal Cancers

Matsuoka,

Yashiro

2023

Biomolecules

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Transforming growth factor-β (TGF-β) has attracted attention as a tumor suppressor because of its potent growth-suppressive effect on epithelial cells. Dysregulation of the TGF-β signaling pathway is considered to be one of the key factors in carcinogenesis, and genetic alterations affecting TGF-β signaling are extraordinarily common in cancers of the gastrointestinal system, such as hereditary nonpolyposis colon cancer and pancreatic cancer. Accumulating evidence suggests that TGF-β is produced from various types of cells in the tumor microenvironment and mediates extracellular matrix deposition, tumor angiogenesis, the formation of CAFs, and suppression of the anti-tumor immune reaction. It is also being considered as a factor that promotes the malignant transformation of cancer, particularly the invasion and metastasis of cancer cells, including epithelial-mesenchymal transition. Therefore, elucidating the role of TGF-β signaling in carcinogenesis, cancer invasion, and metastasis will provide novel basic insight for diagnosis and prognosis and the development of new molecularly targeted therapies for gastrointestinal cancers. In this review, we outline an overview of the complex mechanisms and functions of TGF-β signaling. Furthermore, we discuss the therapeutic potentials of targeting the TGF-β signaling pathway for gastrointestinal cancer treatment and discuss the remaining challenges and future perspectives on targeting this pathway.

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Section: Discussion and Future Perspectivementioning

confidence: 99%

The Role of the Transforming Growth Factor-β Signaling Pathway in Gastrointestinal Cancers

Matsuoka,

Yashiro

2023

Biomolecules

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“…[ 17,18 ] Instead of targeted depletion, the most effective therapeutic paradigm for cancer treatment may be CAF reprogramming through deactivation. [ 19–25 ] However, how to reprogram active CAFs toward deactivated state still keeps immense challenges.…”

Section: Introductionmentioning

confidence: 99%

Perylene‐Mediated Cytoskeletal Dysfunction Remodels Cancer‐Associated Fibroblasts to Augment Antitumor Immunotherapy

Shi,

Lou,

et al. 2024

Adv Healthcare Materials

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Targeted reprogramming cancer‐associated fibroblasts (CAFs) is one of the most essential cancer therapies. However, how to reprogram active CAFs towards deactivated state still remains immense challenges. To tackle this challenge, we herein prepared one perylene PDIC‐OC, which can trigger endogenous reactive oxygen species (ROS) burst to result in cytoskeletal dysfunction and cell apoptosis so that suppress transforming growth factor β (TGF‐β) production. As a result, PDIC‐OC can reprogram the activated CAFs and relieve immunosuppressive tumor microenvironment by efficient polarization of M2‐typed macrophages into M1‐typed ones, down‐regulation of alpha‐smooth muscle actin (α‐SMA), alleviation of hypoxic state to promote infiltration of cytotoxic T lymphocytes, and ultimately realized outstanding anti‐tumor performance on B16F10 tumor‐xenografted and lung‐metastatic mouse model even at low concentration of 1 mg kg−1 body weight. This work thus presents a novel strategy that cytoskeleton dysfunction and cell apoptosis cooperatively suppress the secretion of TGF‐β to reprogram CAFs and meanwhile clarifies intrinsic mechanism for perylene‐triggered chemo‐immunotherapy against hypoxic tumors.This article is protected by copyright. All rights reserved

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“…14,15 The TGF-β pathway has been identified as a significant contributor to glioma development due to its influence on various processes such as tumor cell proliferation, invasion, angiogenesis, and maintenance of stem cell stemness. [16][17][18] Additionally, TGF-β plays a crucial role in driving the immune-suppression of the anti-GBM responses within the TME. 19,20 It regulates a large number of immune cell types and controls both adaptive and innate immunity, thus forming a negative immune regulatory network.…”

Section: Introductionmentioning

confidence: 99%

“…14,15 The TGF-β pathway has been identified as a significant contributor to glioma development due to its influence on various processes such as tumor cell proliferation, invasion, angiogenesis, and maintenance of stem cell stemness. [16][17][18] Additionally, TGF-β plays a crucial role (which was not certified by peer review) is the author/funder. All rights reserved.…”

Section: Introductionmentioning

confidence: 99%

Armored Bicistronic CAR T Cells with Dominant-negative TGF-β Receptor II to Overcome Resistance in Glioblastoma

Li,

Rodriguez,

Yin

et al. 2024

Preprint

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Chimeric antigen receptor (CAR) T cells have shown significant efficacy in hematological diseases. However, CAR T therapy has demonstrated limited efficacy in solid tumors, including glioblastoma (GBM). One of the most important reasons is the immunosuppressive tumor microenvironment (TME), which promotes tumor growth and suppresses immune cells to eliminate tumor cells. The human transforming growth factor-beta (TGF-β) plays a crucial role in forming the suppressive GBM TME and driving the suppression of the anti-GBM response. In order to mitigate TGF-β mediated suppressive activity, we combined a dominant-negative TGF-β receptor II (dnTGFβRII) with our previous bicistronic CART-EGFR-IL13Rα2 construct, currently being evaluated in a clinical trial, to generate CART-EGFR-IL13Rα2-dnTGFβRII, a tri-modular construct we are developing for clinical application. We hypothesized that this approach would more effectively subvert resistance mechanisms observed with GBM. Our data suggests that CART-EGFR-IL13Rα2-dnTGFβRII significantly augmented T cell proliferation and enhanced functional responses, particularly in a TGFβ-rich tumor environment. Additionally, in vivo studies validated the safety and efficacy of the dnTGFβRII cooperating with CARs in targeting and eradicating GBM in a NSG mouse model.

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Small extracellular vesicle TGF-β in cancer progression and immune evasion

Cited by 6 publications

References 128 publications

The Role of the Transforming Growth Factor-β Signaling Pathway in Gastrointestinal Cancers

The Role of the Transforming Growth Factor-β Signaling Pathway in Gastrointestinal Cancers

Perylene‐Mediated Cytoskeletal Dysfunction Remodels Cancer‐Associated Fibroblasts to Augment Antitumor Immunotherapy

Armored Bicistronic CAR T Cells with Dominant-negative TGF-β Receptor II to Overcome Resistance in Glioblastoma

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