Notch Signaling and PD-1/PD-L1 Interaction in Hepatocellular Carcinoma: Potentialities of Combined Therapies

Immunotherapy has shown significant improvement in the survival of patients with hepatocellular carcinoma (HCC) compared to TKIs as first-line treatment. Unfortunately, approximately 30% of HCC exhibits intrinsic resistance to ICIs, making new therapeutic combinations urgently needed. The dysregulat...

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Main Authors: Annapaola Montagner, Andrea Arleo, Fabrizia Suzzi, Antonino B. D’Assoro, Fabio Piscaglia, Laura Gramantieri, Catia Giovannini
Format: Article
Language:English
Published: MDPI AG 2024-12-01
Series:Biomolecules
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Online Access:https://www.mdpi.com/2218-273X/14/12/1581
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author Annapaola Montagner
Andrea Arleo
Fabrizia Suzzi
Antonino B. D’Assoro
Fabio Piscaglia
Laura Gramantieri
Catia Giovannini
author_facet Annapaola Montagner
Andrea Arleo
Fabrizia Suzzi
Antonino B. D’Assoro
Fabio Piscaglia
Laura Gramantieri
Catia Giovannini
author_sort Annapaola Montagner
collection DOAJ
description Immunotherapy has shown significant improvement in the survival of patients with hepatocellular carcinoma (HCC) compared to TKIs as first-line treatment. Unfortunately, approximately 30% of HCC exhibits intrinsic resistance to ICIs, making new therapeutic combinations urgently needed. The dysregulation of the Notch signaling pathway observed in HCC can affect immune cell response, reducing the efficacy of cancer immunotherapy. Here, we provide an overview of how Notch signaling regulates immune responses and present the therapeutic rationale for combining Notch signaling inhibition with ICIs to improve HCC treatment. Moreover, we propose using exosomes as non-invasive tools to assess Notch signaling activation in hepatic cancer cells, enabling accurate stratification of patients who can benefit from combined strategies.
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spelling doaj-art-267a97bd03794ddebacf693a2607690d2025-08-20T02:56:06ZengMDPI AGBiomolecules2218-273X2024-12-011412158110.3390/biom14121581Notch Signaling and PD-1/PD-L1 Interaction in Hepatocellular Carcinoma: Potentialities of Combined TherapiesAnnapaola Montagner0Andrea Arleo1Fabrizia Suzzi2Antonino B. D’Assoro3Fabio Piscaglia4Laura Gramantieri5Catia Giovannini6Department of Medical and Surgical Sciences, Bologna University, 40138 Bologna, ItalyDepartment of Medical and Surgical Sciences, Bologna University, 40138 Bologna, ItalyDepartment of Medical and Surgical Sciences, Bologna University, 40138 Bologna, ItalyDepartment of Oncology, Mayo Clinic College of Medicine, Rochester, MN 55902, USADepartment of Medical and Surgical Sciences, Bologna University, 40138 Bologna, ItalyDivision of Internal Medicine, Hepatobiliary and Immunoallergic Diseases, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, ItalyDepartment of Medical and Surgical Sciences, Bologna University, 40138 Bologna, ItalyImmunotherapy has shown significant improvement in the survival of patients with hepatocellular carcinoma (HCC) compared to TKIs as first-line treatment. Unfortunately, approximately 30% of HCC exhibits intrinsic resistance to ICIs, making new therapeutic combinations urgently needed. The dysregulation of the Notch signaling pathway observed in HCC can affect immune cell response, reducing the efficacy of cancer immunotherapy. Here, we provide an overview of how Notch signaling regulates immune responses and present the therapeutic rationale for combining Notch signaling inhibition with ICIs to improve HCC treatment. Moreover, we propose using exosomes as non-invasive tools to assess Notch signaling activation in hepatic cancer cells, enabling accurate stratification of patients who can benefit from combined strategies.https://www.mdpi.com/2218-273X/14/12/1581NotchPD-1PD-L1hepatocellular carcinoma (HCC)immunotherapycombination therapy
spellingShingle Annapaola Montagner
Andrea Arleo
Fabrizia Suzzi
Antonino B. D’Assoro
Fabio Piscaglia
Laura Gramantieri
Catia Giovannini
Notch Signaling and PD-1/PD-L1 Interaction in Hepatocellular Carcinoma: Potentialities of Combined Therapies
Biomolecules
Notch
PD-1
PD-L1
hepatocellular carcinoma (HCC)
immunotherapy
combination therapy
title Notch Signaling and PD-1/PD-L1 Interaction in Hepatocellular Carcinoma: Potentialities of Combined Therapies
title_full Notch Signaling and PD-1/PD-L1 Interaction in Hepatocellular Carcinoma: Potentialities of Combined Therapies
title_fullStr Notch Signaling and PD-1/PD-L1 Interaction in Hepatocellular Carcinoma: Potentialities of Combined Therapies
title_full_unstemmed Notch Signaling and PD-1/PD-L1 Interaction in Hepatocellular Carcinoma: Potentialities of Combined Therapies
title_short Notch Signaling and PD-1/PD-L1 Interaction in Hepatocellular Carcinoma: Potentialities of Combined Therapies
title_sort notch signaling and pd 1 pd l1 interaction in hepatocellular carcinoma potentialities of combined therapies
topic Notch
PD-1
PD-L1
hepatocellular carcinoma (HCC)
immunotherapy
combination therapy
url https://www.mdpi.com/2218-273X/14/12/1581
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