Immune checkpoint molecules are regulated by transforming growth factor (TGF)-<i>β</i>1-induced epithelial-to-mesenchymal transition in hepatocellular carcinoma

Shrestha, Ritu; Bridle, Kim R.; Crawford, Darrell H. G.; Jayachandran, Aparna

doi:10.7150/ijms.54239

Cited by 17 publications

(8 citation statements)

References 89 publications

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“…TGF-β is highly expressed in HCC, in which cancer-associated fibroblasts (CAFs) derived from stromal cells or hepatocytes are the principal source of TGF-β ( 109 ). TGF-β upregulates the expression of transcription repressor Snail and downregulates E-cadherin in HCC to promote EMT, as well as tumor invasion and metastasis, supporting the role of TGF-β in tumor progression and poor patient prognosis ( 110 ).…”

Section: Action Mechanism Of Iqgaps In Hccmentioning

confidence: 83%

Role of IQ Motif-Containing GTPase-Activating Proteins in Hepatocellular Carcinoma

et al. 2022

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IQ motif-containing GTPase-activating proteins (IQGAPs) are a class of scaffolding proteins, including IQGAP1, IQGAP2, and IQGAP3, which govern multiple cellular activities by facilitating cytoskeletal remodeling and cellular signal transduction. The role of IQGAPs in cancer initiation and progression has received increasing attention in recent years, especially in hepatocellular carcinoma (HCC), where the aberrant expression of IQGAPs is closely related to patient prognosis. IQGAP1 and 3 are upregulated and are considered oncogenes in HCC, while IQGAP2 is downregulated and functions as a tumor suppressor. This review details the three IQGAP isoforms and their respective structures. The expression and role of each protein in different liver diseases and mainly in HCC, as well as the underlying mechanisms, are also presented. This review also provides a reference for further studies on IQGAPs in HCC.

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Section: Action Mechanism Of Iqgaps In Hccmentioning

confidence: 83%

Role of IQ Motif-Containing GTPase-Activating Proteins in Hepatocellular Carcinoma

et al. 2022

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“…For example, PD-L1 could be upregulated in ZEB1 and miR-200 dependent manners EMT-activated human breast cancer cells [ 34 ]. In addition, immune checkpoint molecules PD-L1 and B7–H3 were notably upregulated during TGF- β 1-induced EMT [ 35 ]. Although our current study suggested potential relationships of CDCP1 to these pathways, the lack of confirmation from the molecular biology level remained an unavoidable shortcoming of this study.…”

Section: Discussionmentioning

confidence: 99%

Overexpression of CDCP1 is Associated with Poor Prognosis and Enhanced Immune Checkpoints Expressions in Breast Cancer

Zhao

Mei

Wang

et al. 2022

Journal of Oncology

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CUB-domain containing protein 1 (CDCP1) is a transmembrane protein acting as an effector of SRC family kinases, which play an oncogenic role in multiple human cancers. However, its clinical and immune correlations in breast cancer (BrCa) have not been explored. To define the expression, prognostic value, and potential molecular role of CDCP1 in BrCa, multiple public datasets, and an in-house cohort were used. Compared with paratumor tissue, CDCP1 was remarkably upregulated in the tumor tissues at both mRNA and protein levels. In the in-house cohort, CDCP1 protein expression was related to several clinicopathological parameters, including age, ER status, PR status, molecular type, and survival status. Kaplan–Meier analysis and Cox regression analysis exhibited that CDCP1 was an important prognostic biomarker in BrCa. In addition, enrichment analysis uncovered that CDCP1 was not only involved in multiple oncogenic pathways, but correlated with overexpression of immune checkpoints. Overall, we reported that increased expression of CDCP1 is a favorable prognostic factor in patients with BrCa. In addition, the correlations between CDCP1 and immune checkpoints provide a novel insight into the adjuvant treatment for immune checkpoint blockade via targeting CDCP1.

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“…These B7-H3 pro-metastatic effects primarily stem from upregulated expression and activity of MMP2/MMP9, as well as from promotion of EMT transition via the JAK2/STAT3/SLUG signaling [ 49 ]. Shrestha et al showed siRNA-mediated knockdown of B7-H3 reversed TGF- β 1 driven EMT and significantly restricted HCC metastatic potential [ 75 ]. According to the Cancer Genome Atlas—Liver Hepatocellular Carcinoma (TCGA-LIHC) database, HCC prognosis was significantly worse in subjects with the CD8 + T-cell-low/B7-H3-high immunophenotype compared to other immunophenotypes [ 76 ].…”

Section: Hepatopancreatic and Gastrointestinal Malignanciesmentioning

confidence: 99%

New Emerging Targets in Cancer Immunotherapy: The Role of B7-H3

Koumprentziotis,

Theocharopoulos,

Foteinou

et al. 2024

Vaccines

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Immune checkpoints (ICs) are molecules implicated in the fine-tuning of immune response via co-inhibitory or co-stimulatory signals, and serve to secure minimized host damage. Targeting ICs with various therapeutic modalities, including checkpoint inhibitors/monoclonal antibodies (mAbs), antibody-drug conjugates (ADCs), and CAR-T cells has produced remarkable results, especially in immunogenic tumors, setting a paradigm shift in cancer therapeutics through the incorporation of these IC-targeted treatments. However, the large proportion of subjects who experience primary or secondary resistance to available IC-targeted options necessitates further advancements that render immunotherapy beneficial for a larger patient pool with longer duration of response. B7-H3 (B7 Homolog 3 Protein, CD276) is a member of the B7 family of IC proteins that exerts pleiotropic immunomodulatory effects both in physiologic and pathologic contexts. Mounting evidence has demonstrated an aberrant expression of B7-H3 in various solid malignancies, including tumors less sensitive to current immunotherapeutic options, and has associated its expression with advanced disease, worse patient survival and impaired response to IC-based regimens. Anti-B7-H3 agents, including novel mAbs, bispecific antibodies, ADCs, CAR-T cells, and radioimmunotherapy agents, have exhibited encouraging antitumor activity in preclinical models and have recently entered clinical testing for several cancer types. In the present review, we concisely present the functional implications of B7-H3 and discuss the latest evidence regarding its prognostic significance and therapeutic potential in solid malignancies, with emphasis on anti-B7-H3 modalities that are currently evaluated in clinical trial settings. Better understanding of B7-H3 intricate interactions in the tumor microenvironment will expand the oncological utility of anti-B7-H3 agents and further shape their role in cancer therapeutics.

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Immune checkpoint molecules are regulated by transforming growth factor (TGF)-β1-induced epithelial-to-mesenchymal transition in hepatocellular carcinoma

Cited by 17 publications

References 89 publications

Role of IQ Motif-Containing GTPase-Activating Proteins in Hepatocellular Carcinoma

Role of IQ Motif-Containing GTPase-Activating Proteins in Hepatocellular Carcinoma

Overexpression of CDCP1 is Associated with Poor Prognosis and Enhanced Immune Checkpoints Expressions in Breast Cancer

New Emerging Targets in Cancer Immunotherapy: The Role of B7-H3

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