Chamma Hanane, Vila Isabelle K, Taffoni Clara, Turtoi Andrei, Laguette Nadine
Institut de Génétique Humaine, CNRS, Université de Montpellier, Molecular Basis of Inflammation Laboratory, Montpellier, France.
Tumor Microenvironment Laboratory, Institut de Recherche en Cancérologie de Montpellier, Université de Montpellier, INSERM U1194, 34000, Montpellier, France.
Cancer Lett. 2022 Jul 10;538:215694. doi: 10.1016/j.canlet.2022.215694. Epub 2022 Apr 27.
Pancreatic ductal adenocarcinoma (PDAC) is a cancer of poor prognosis that presents with a dense desmoplastic stroma that contributes to therapeutic failure. PDAC patients are mostly unresponsive to immunotherapy. However, hopes to elicit response to immunotherapy have emerged with novel strategies targeting the Stimulator of Interferon Genes (STING) protein, which is a major regulator of tumor-associated inflammation. Combination of STING agonists with conventional immunotherapy approaches has proven to potentiate therapeutic benefits in several cancers. However, recent data underscore that the output of STING activation varies depending on the cellular and tissue context. This suggests that tumor heterogeneity, and in particular the heterogeneity of the tumor microenvironment (TME), is a key factor determining whether STING activation would bear benefits for patients. In this review, we discuss the potential benefits of STING activation in PDAC. To this aim, we describe the major components of the PDAC TME, and the expected consequences of STING activation.
胰腺导管腺癌（PDAC）是一种预后较差的癌症，其特征是存在致密的促纤维增生性基质，这会导致治疗失败。PDAC患者大多对免疫疗法无反应。然而，随着针对干扰素基因刺激物（STING）蛋白的新策略的出现，人们对免疫疗法产生反应的希望也随之而来，STING蛋白是肿瘤相关炎症的主要调节因子。在几种癌症中，STING激动剂与传统免疫疗法相结合已被证明能增强治疗效果。然而，最近的数据强调，STING激活的结果因细胞和组织背景而异。这表明肿瘤异质性，尤其是肿瘤微环境（TME）的异质性，是决定STING激活是否对患者有益的关键因素。在这篇综述中，我们讨论了STING激活在PDAC中的潜在益处。为此，我们描述了PDAC TME的主要成分，以及STING激活的预期后果。
