Garnier Jonathan, Turrini Olivier, Chretien Anne-Sophie, Olive Daniel
Departement of Surgical Oncology, Institut Paoli-Calmettes, 232 Boulevard de Sainte Marguerite, 13009 Marseille, France.
Centre de Recherche en Cancérologie de Marseille, Aix-Marseille University, 58 Boulevard Charles Livon, 13007 Marseille, France.
J Clin Med. 2022 Mar 31;11(7):1948. doi: 10.3390/jcm11071948.
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.
胰腺导管腺癌（PDAC）仍然是主要的致死病因，且由于治疗效果不尽人意，其生存情况堪忧，是一个具有挑战性的临床研究问题。两个主要问题阻碍了局部晚期不可切除胰腺癌（LAPC）的治疗：高微转移率和手术不可及性。局部消融疗法除了产生局部效应外，还能引发全身抗肿瘤反应（即远隔效应）。因此，联合其他疗法可能是提高免疫疗法临床疗效的关键。在本系统评价中，我们探讨了局部消融疗法联合免疫疗法在克服PDAC免疫抵抗方面的最新应用，并讨论了未来的前景和挑战。特别是，我们描述了四项放化疗研究和九篇关于不可逆电穿孔（IRE）的报告。临床上，IRE是首选的消融疗法，除两项临床试验外，其他所有临床试验均有应用，并且可能为免疫疗法创造有利的微环境。多种免疫疗法已与IRE联合使用，如基于NK细胞或γδT细胞的疗法，以及免疫检查点抑制剂。本综述中呈现的临床试验结果以及这些疗法推进至II/III期试验的潜力仍不明确。一种涉及化疗、局部消融和免疫疗法的多治疗方法有望克服LAPC的双重难题。
