Local Ablative Therapy Associated with Immunotherapy in Locally Advanced Pancreatic Cancer: A Solution to Overcome the Double Trouble?—A Comprehensive Review

Pancreatic ductal adenocarcinoma (PDAC) remains a major killer and is a challenging clinical research issue with abysmal survival due to unsatisfactory therapeutic efficacy. Two major issues thwart the treatment of locally advanced nonresectable pancreatic cancer (LAPC): high micrometastasis rate an...

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Main Authors: Jonathan Garnier, Olivier Turrini, Anne-Sophie Chretien, Daniel Olive
Format: Article
Language:English
Published: MDPI AG 2022-03-01
Series:Journal of Clinical Medicine
Subjects:
Online Access:https://www.mdpi.com/2077-0383/11/7/1948
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author Jonathan Garnier
Olivier Turrini
Anne-Sophie Chretien
Daniel Olive
author_facet Jonathan Garnier
Olivier Turrini
Anne-Sophie Chretien
Daniel Olive
author_sort Jonathan Garnier
collection DOAJ
description Pancreatic ductal adenocarcinoma (PDAC) remains a major killer and is a challenging clinical research issue with abysmal survival due to unsatisfactory therapeutic efficacy. Two major issues thwart the treatment of locally advanced nonresectable pancreatic cancer (LAPC): high micrometastasis rate and surgical inaccessibility. Local ablative therapies induce a systemic antitumor response (i.e., abscopal effect) in addition to local effects. Thus, the incorporation of additional therapies could be key to improving immunotherapy’s clinical efficacy. In this systematic review, we explore recent applications of local ablative therapies combined with immunotherapy to overcome immune resistance in PDAC and discuss future perspectives and challenges. Particularly, we describe four chemoradiation studies and nine reports on irreversible electroporation (IRE). Clinically, IRE is the ablative therapy of choice, utilized in all but two clinical trials, and may create a favorable microenvironment for immunotherapy. Various immunotherapies have been used in combination with IRE, such as NK cell- or γδ T cell-based therapy, as well as immune checkpoint inhibitors. The results of the clinical trials presented in this review and the advancement potential of these therapies to phase II/III trials remain unknown. A multiple treatment approach involving chemotherapy, local ablation, and immunotherapy holds promise in overcoming the double trouble of LAPC.
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spelling doaj.art-7644d77984f346859082c62dee7bd97f2023-11-30T23:29:04ZengMDPI AGJournal of Clinical Medicine2077-03832022-03-01117194810.3390/jcm11071948Local Ablative Therapy Associated with Immunotherapy in Locally Advanced Pancreatic Cancer: A Solution to Overcome the Double Trouble?—A Comprehensive ReviewJonathan Garnier0Olivier Turrini1Anne-Sophie Chretien2Daniel Olive3Departement of Surgical Oncology, Institut Paoli-Calmettes, 232 Boulevard de Sainte Marguerite, 13009 Marseille, FranceDepartement of Surgical Oncology, Institut Paoli-Calmettes, 232 Boulevard de Sainte Marguerite, 13009 Marseille, FranceCentre de Recherche en Cancérologie de Marseille, Aix-Marseille University, 58 Boulevard Charles Livon, 13007 Marseille, FranceCentre de Recherche en Cancérologie de Marseille, Aix-Marseille University, 58 Boulevard Charles Livon, 13007 Marseille, FrancePancreatic ductal adenocarcinoma (PDAC) remains a major killer and is a challenging clinical research issue with abysmal survival due to unsatisfactory therapeutic efficacy. Two major issues thwart the treatment of locally advanced nonresectable pancreatic cancer (LAPC): high micrometastasis rate and surgical inaccessibility. Local ablative therapies induce a systemic antitumor response (i.e., abscopal effect) in addition to local effects. Thus, the incorporation of additional therapies could be key to improving immunotherapy’s clinical efficacy. In this systematic review, we explore recent applications of local ablative therapies combined with immunotherapy to overcome immune resistance in PDAC and discuss future perspectives and challenges. Particularly, we describe four chemoradiation studies and nine reports on irreversible electroporation (IRE). Clinically, IRE is the ablative therapy of choice, utilized in all but two clinical trials, and may create a favorable microenvironment for immunotherapy. Various immunotherapies have been used in combination with IRE, such as NK cell- or γδ T cell-based therapy, as well as immune checkpoint inhibitors. The results of the clinical trials presented in this review and the advancement potential of these therapies to phase II/III trials remain unknown. A multiple treatment approach involving chemotherapy, local ablation, and immunotherapy holds promise in overcoming the double trouble of LAPC.https://www.mdpi.com/2077-0383/11/7/1948locally advanced pancreatic cancerirreversible electroporationimmunotherapyimmune checkpoint inhibitor
spellingShingle Jonathan Garnier
Olivier Turrini
Anne-Sophie Chretien
Daniel Olive
Local Ablative Therapy Associated with Immunotherapy in Locally Advanced Pancreatic Cancer: A Solution to Overcome the Double Trouble?—A Comprehensive Review
Journal of Clinical Medicine
locally advanced pancreatic cancer
irreversible electroporation
immunotherapy
immune checkpoint inhibitor
title Local Ablative Therapy Associated with Immunotherapy in Locally Advanced Pancreatic Cancer: A Solution to Overcome the Double Trouble?—A Comprehensive Review
title_full Local Ablative Therapy Associated with Immunotherapy in Locally Advanced Pancreatic Cancer: A Solution to Overcome the Double Trouble?—A Comprehensive Review
title_fullStr Local Ablative Therapy Associated with Immunotherapy in Locally Advanced Pancreatic Cancer: A Solution to Overcome the Double Trouble?—A Comprehensive Review
title_full_unstemmed Local Ablative Therapy Associated with Immunotherapy in Locally Advanced Pancreatic Cancer: A Solution to Overcome the Double Trouble?—A Comprehensive Review
title_short Local Ablative Therapy Associated with Immunotherapy in Locally Advanced Pancreatic Cancer: A Solution to Overcome the Double Trouble?—A Comprehensive Review
title_sort local ablative therapy associated with immunotherapy in locally advanced pancreatic cancer a solution to overcome the double trouble a comprehensive review
topic locally advanced pancreatic cancer
irreversible electroporation
immunotherapy
immune checkpoint inhibitor
url https://www.mdpi.com/2077-0383/11/7/1948
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