Solimando Antonio Giovanni, Summa Simona De, Vacca Angelo, Ribatti Domenico
Department of Biomedical Sciences and Human Oncology, Section of Internal Medicine 'G. Baccelli', University of Bari Medical School, 70124 Bari, Italy.
Istituto di Ricovero e Cura a Carattere Scientifico-IRCCS Istituto Tumori "Giovanni Paolo II" of Bari, 70124 Bari, Italy.
Cancers (Basel). 2020 Nov 15;12(11):3380. doi: 10.3390/cancers12113380.
Cancer-associated neo vessels' formation acts as a gatekeeper that orchestrates the entrance and egress of patrolling immune cells within the tumor milieu. This is achieved, in part, via the directed chemokines' expression and cell adhesion molecules on the endothelial cell surface that attract and retain circulating leukocytes. The crosstalk between adaptive immune cells and the cancer endothelium is thus essential for tumor immune surveillance and the success of immune-based therapies that harness immune cells to kill tumor cells. This review will focus on the biology of the endothelium and will explore the vascular-specific molecular mediators that control the recruitment, retention, and trafficking of immune cells that are essential for effective antitumor immunity. The literature revision will also explore how abnormalities in the tumor endothelium impair crosstalk with adaptive immune cells and how targeting these abnormalities can improve the success of immune-based therapies for different malignancies, with a particular focus on the paradigmatic example represented by multiple myeloma. We also generated and provide two original bio-informatic analyses, in order to sketch the physiopathology underlying the endothelial-neoplastic interactions in an easier manner, feeding into a vicious cycle propagating disease progression and highlighting novel pathways that might be exploited therapeutically.
癌症相关新生血管的形成充当了一个守门人，它协调着肿瘤微环境中巡逻免疫细胞的进出。这部分是通过内皮细胞表面趋化因子的定向表达和细胞黏附分子来实现的，这些趋化因子和黏附分子能够吸引并留住循环中的白细胞。因此，适应性免疫细胞与癌症内皮细胞之间的相互作用对于肿瘤免疫监视以及利用免疫细胞杀死肿瘤细胞的免疫疗法的成功至关重要。本综述将聚焦于内皮细胞的生物学特性，并探讨血管特异性分子介质，这些介质控制着免疫细胞的募集、滞留和运输，而这些对于有效的抗肿瘤免疫至关重要。文献综述还将探讨肿瘤内皮细胞的异常如何损害与适应性免疫细胞的相互作用，以及针对这些异常如何提高针对不同恶性肿瘤的免疫疗法的成功率，尤其关注以多发性骨髓瘤为代表的典型例子。我们还进行并提供了两项原创的生物信息学分析，以便更轻松地勾勒内皮细胞与肿瘤细胞相互作用的病理生理学基础，揭示推动疾病进展的恶性循环，并突出可能用于治疗的新途径。
