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doi:10.18632/oncotarget.v7i47

Cited by 10 publications

(6 citation statements)

References 11 publications

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“…First, high serum sPD-L1 is a predictor of poor response to PD-1 inhibition in some malignancies and predicts poor outcomes overall in hepatocellular carcinoma, cholangiocarcinoma, lung cancer, melanoma, myeloma, NK T cell lymphoma, and others. [29][30][31][32][33][34][35][36][37] Tumor ADAM10 and ADAM17 cleave sPD-L1 that may mediate this PD-1 inhibitor resistance by inducing CD8 + T cell death. sPD-L1 may also act as a sink for circulating PD-L1 inhibitors (see Figure 4(e)).…”

Section: Discussionmentioning

confidence: 99%

ADAM10 and ADAM17 cleave PD-L1 to mediate PD-(L)1 inhibitor resistance

et al. 2020

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2020) ADAM10 and ADAM17 cleave PD-L1 to mediate PD-(L)1 inhibitor resistance, ABSTRACT ADAM10 and ADAM17 expression and soluble PD-L1 (sPD-L1) predict poor prognosis in many malignancies, including in patients treated with PD-(L)1 inhibitors. The mechanism of soluble PD-L1 production and its effects are unknown. Here we uncover a novel mechanism of ADAM10-and ADAM17-mediated resistance to PD-(L)1 inhibitors. ADAM10 and ADAM17 cleave PD-L1 from the surface of malignant cells and extracellular vesicles. This cleavage produces an active sPD-L1 fragment that induces apoptosis in CD8 + T cells and compromises the killing of tumor cells by CD8 + T cells. Reduced tumor site PD-L1 protein-to-mRNA ratios predict poor outcomes and are correlated with elevated ADAM10 and ADAM17 expression in multiple cancers. These results may explain the discordance between PD-L1 immunohistochemistry and PD-(L)1 inhibitor response. Thus, including ADAM10 and ADAM17 tissue staining may improve therapy selection. Furthermore, treatment with an ADAM10/ADAM17 inhibitor may abrogate PD-(L)1 inhibitor resistance and improve clinical responses to PD-(L)1 immunotherapy. ARTICLE HISTORY Materials and methods Cell cultureMalignant cell lines 786-0, Karpas-299, and Du145 (ATCC) were grown in RPMI 1640 (Invitrogen) supplemented by 10%

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Section: Discussionmentioning

confidence: 99%

ADAM10 and ADAM17 cleave PD-L1 to mediate PD-(L)1 inhibitor resistance

et al. 2020

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“…The misregulation of APN expression has also been observed in a wide range of human malignancies and cancers such as cancer of colon, ovary, cervix, prostate, breast, liver and melanoma, renal cell carcinoma (RCC), hepatocellular carcinoma, etc. Importantly, APN is not just responsible for cellular proliferation and angiogenesis but also affects the cell invasion and metastasis [1,2,4,[13][14][15][16][17][18][19][20][21][22][23][24][25][26].…”

Section: Introductionmentioning

confidence: 99%

Exploring the structural aspects of ureido-amino acid-based APN inhibitors: a validated comparative multi-QSAR modelling study

Banerjee

Amin

Baidya

et al. 2020

SAR and QSAR in Environmental Research

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The zinc-dependent enzyme aminopeptidase N (APN) is a member of the M1 metalloenzyme family. The multi-functionality of APN as a peptidase, a receptor and a signalling molecule has provided it the access to influence a number of disease conditions namely viral diseases, angiogenesis, cellular metastasis and invasion including different cancer conditions. Hence, the development of potent APN inhibitors is a possible route for the treatment of diseases related to the activity of APN. In this study, different QSAR approaches have been adopted to identify the structural features of a group of hydroxamate-based ureido-amino acid derivative APN inhibitors. This study was able to identify different constitutional aspects of these APN inhibitors which are important for their inhibitory potency. Additionally, some of these observations were also aligned with the observations of previously performed QSAR studies conducted on different APN inhibitors. Therefore, the results of this study may help to design potent and effective APN inhibitors in the future. ARTICLE HISTORY

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“…Such genes included the regulators of B cell receptor signaling Dgka and Cblb , already discussed above ( Figures 6D, E ) ( 91 – 93 ). The genes also included Litaf that encodes a repressor of Bcl6 -expression and a regulator of autophagy and apoptosis in B cell lymphoma ( 94 , 95 ), as well as Igf2bp3 that encodes a reader of the N6-methyladenosine (m6A) RNA-modification, specifically induced in GC B cells and essential for normal induction of humoral immune response ( Figures 6D, E ) ( 96 ). In summary, our study identifies novel transcriptional targets of BAP1 that are essential for the progression of GC-reaction and can contribute to the failure of humoral immunity with the loss of BAP1 function.…”

Section: Resultsmentioning

confidence: 99%

B-cell intrinsic regulation of antibody mediated immunity by histone H2A deubiquitinase BAP1

Liang,

Wang,

Seija

et al. 2024

Front. Immunol.

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IntroductionBAP1 is a deubiquitinase (DUB) of the Ubiquitin C-terminal Hydrolase (UCH) family that regulates gene expression and other cellular processes, through its direct catalytic activity on the repressive epigenetic mark histone H2AK119ub, as well as on several other substrates. BAP1 is also a highly important tumor suppressor, expressed and functional across many cell types and tissues. In recent work, we demonstrated a cell intrinsic role of BAP1 in the B cell lineage development in murine bone marrow, however the role of BAP1 in the regulation of B cell mediated humoral immune response has not been previously explored. Methods and resultsIn the current study, we demonstrate that a B-cell intrinsic loss of BAP1 in activated B cells in the Bap1fl/flCγ1-cre murine model results in a severe defect in antibody production, with altered dynamics of germinal centre B cell, memory B cell, and plasma cell numbers. At the cellular and molecular level, BAP1 was dispensable for B cell immunoglobulin class switching but resulted in an impaired proliferation of activated B cells, with genome-wide dysregulation in histone H2AK119ub levels and gene expression. Conclusion and discussionIn summary, our study establishes the B-cell intrinsic role of BAP1 in antibody mediated immune response and indicates its central role in the regulation of the genome-wide landscapes of histone H2AK119ub and downstream transcriptional programs of B cell activation and humoral immunity.

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Untitled

Cited by 10 publications

References 11 publications

ADAM10 and ADAM17 cleave PD-L1 to mediate PD-(L)1 inhibitor resistance

ADAM10 and ADAM17 cleave PD-L1 to mediate PD-(L)1 inhibitor resistance

Exploring the structural aspects of ureido-amino acid-based APN inhibitors: a validated comparative multi-QSAR modelling study

B-cell intrinsic regulation of antibody mediated immunity by histone H2A deubiquitinase BAP1

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