Targeting ubiquitin-specific protease-7 in plasmacytoid dendritic cells triggers anti-myeloma immunity

Ray, Arghya; Du, Ting; Song, Yan; Buhrlage, Sara J.; Chauhan, Dharminder; Anderson, Kenneth C.

doi:10.1038/s41375-021-01129-0

Cited by 4 publications

(4 citation statements)

References 15 publications

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“…Consistently, USP7 knockdown destabilized FOXP3 and reversed Treg‐induced immune deficits in vitro and in vivo, facilitating immune‐mediated tumor regression 137,138 . An investigation performed by Ray et al discovered that pharmacological inhibition of USP7 restored innate and adaptive immune responses in multiple myeloma through activating plasmacytoid dendritic cells, triggering multiple myeloma‐specific cytotoxic T lymphocytes and natural killer cells, and decreasing abnormal Tregs 139 . On the other hand, USP7 may function as a tumor suppressor via p53 regulation.…”

Section: The Role Of Ups Dysregulation In Tumorigenesismentioning

confidence: 95%

“…137,138 An investigation performed by Ray et al discovered that pharmacological inhibition of USP7 restored innate and adaptive immune responses in multiple myeloma through activating plasmacytoid dendritic cells, triggering multiple myeloma-specific cytotoxic T lymphocytes and natural killer cells, and decreasing abnormal Tregs. 139 On the other hand, USP7 may function as a tumor suppressor via p53 regulation. Intriguing research by Niu et al revealed that irradiation-induced USP7 decreased the radioresistance of mutated p53 laryngeal squamous cell carcinoma (LSCC) while improving the radioresistance of normal cells with wild-type p53.…”

Section: Deubiquitinasesmentioning

confidence: 99%

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Modulation of the ubiquitin‐proteasome system by phytochemicals: Therapeutic implications in malignancies with an emphasis on brain tumors

et al. 2023

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Regarding the multimechanistic nature of cancers, current chemo‐ or radiotherapies often fail to eradicate disease pathology, and frequent relapses or resistance to therapies occur. Brain malignancies, particularly glioblastomas, are difficult‐to‐treat cancers due to their highly malignant and multidimensional biology. Unfortunately, patients suffering from malignant tumors often experience poor prognoses and short survival periods. Thus far, significant efforts have been conducted to discover novel and more effective modalities. To that end, modulation of the ubiquitin‐proteasome system (UPS) has attracted tremendous interest since it affects the homeostasis of proteins critically engaged in various cell functions, for example, cell metabolism, survival, proliferation, and differentiation. With their safe and multimodal actions, phytochemicals are among the promising therapeutic tools capable of turning the operation of various UPS elements. The present review, along with an updated outline of the role of UPS dysregulation in multiple cancers, provided a detailed discussion on the impact of phytochemicals on the UPS function in malignancies, especially brain tumors.

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Section: The Role Of Ups Dysregulation In Tumorigenesismentioning

confidence: 95%

Section: Deubiquitinasesmentioning

confidence: 99%

Modulation of the ubiquitin‐proteasome system by phytochemicals: Therapeutic implications in malignancies with an emphasis on brain tumors

et al. 2023

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“…17 not only restore adaptive immunity through modulation of Tregs and CD8 + T cells but also promote innate immunity through effects on natural killer (NK) cells, plasmacytoid dendritic cells (pDCs), and macrophages. 18,19 Collectively, USP7 inhibitors hold a great promise for cancer immunotherapy.…”

Section: ■ Introductionmentioning

confidence: 99%

“…Wang et al reported that USP7 inhibitors downregulated PD-L1 expression to enhance the antitumor immune response in gastric cancer . Interestingly, pharmacological inhibition of USP7 can not only restore adaptive immunity through modulation of Tregs and CD8 + T cells but also promote innate immunity through effects on natural killer (NK) cells, plasmacytoid dendritic cells (pDCs), and macrophages. , Collectively, USP7 inhibitors hold a great promise for cancer immunotherapy.…”

Section: Introductionmentioning

confidence: 99%

Discovery of Orally Bioavailable N-Benzylpiperidinol Derivatives as Potent and Selective USP7 Inhibitors with In Vivo Antitumor Immunity Activity against Colon Cancer

Yang

Zhang

et al. 2022

J. Med. Chem.

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USP7 emerges as a potential therapeutic target for cancers, as it plays an important role in the development of tumorigenesis by stabilizing multiple cancer-relevant proteins. Nevertheless, the discovery of drug-like USP7 inhibitors remains challenging. Herein, we report a series of N-benzylpiperidinol derivatives as potent and selective USP7 inhibitors (e.g., X20 and X26: IC50 = 7.6 and 8.2 nM), whose binding modes were revealed by crystallographic studies to be distinct from the known N-acylpiperidinol USP7 inhibitors. Among them, X36 with good oral PK profiles (rat: F = 40.8% and T 1/2 = 3.5 h) exhibited significant antitumor efficacy in the MC38 colon cancer syngeneic mouse model, at least partly through upregulating the tumor infiltration of CD8+ T, NK, and NKT cells and downregulating that of Tregs and MDSCs. These findings may further pave the way for the development of USP7 inhibitors as novel cancer immunotherapy drugs.

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Targeting the ubiquitin pathway in lymphoid malignancies

Li,

Adam Eichhorn,

Chng

2024

Cancer Letters

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Targeting ubiquitin-specific protease-7 in plasmacytoid dendritic cells triggers anti-myeloma immunity

Cited by 4 publications

References 15 publications

Modulation of the ubiquitin‐proteasome system by phytochemicals: Therapeutic implications in malignancies with an emphasis on brain tumors

Modulation of the ubiquitin‐proteasome system by phytochemicals: Therapeutic implications in malignancies with an emphasis on brain tumors

Discovery of Orally Bioavailable N-Benzylpiperidinol Derivatives as Potent and Selective USP7 Inhibitors with In Vivo Antitumor Immunity Activity against Colon Cancer

Targeting the ubiquitin pathway in lymphoid malignancies

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