Roberto Michela, Arrivi Giulia, Di Civita Mattia Alberto, Barchiesi Giacomo, Pilozzi Emanuela, Marchetti Paolo, Santini Daniele, Mazzuca Federica, Tomao Silverio
Oncology Unit (UOC) Oncologia A, Department of Radiological, Oncological and Anathomo-patological Science, Policlinico Umberto I, Sapienza University of Rome, Rome, Italy.
Oncology Unit, Department of Clinical and Molecular Medicine, Sant' Andrea University Hospital, Sapienza University of Rome, Rome, Italy.
Front Oncol. 2023 Mar 23;13:1154581. doi: 10.3389/fonc.2023.1154581. eCollection 2023.
Chemokines are small, secreted peptides involved in the mediation of the immune cell recruitment. Chemokines have been implicated in several diseases including autoimmune diseases, viral infections and also played a critical role in the genesis and development of several malignant tumors. CXCL12 is a homeostatic CXC chemokine involved in the process of proliferation, and tumor spread. Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive tumors, that is still lacking effective therapies and with a dramatically poor prognosis.
We conducted a scientific literature search on Pubmed and Google Scholar including retrospective, prospective studies and reviews focused on the current research elucidating the emerging role of CXCL12 and its receptors CXCR4 - CXCR7 in the pathogenesis of pancreatic cancer.
Considering the mechanism of immunomodulation of the CXCL12-CXCR4-CXCR7 axis, as well as the potential interaction with the microenvironment in the PDAC, several combined therapeutic approaches have been studied and developed, to overcome the "cold" immunological setting of PDAC, like combining CXCL12 axis inhibitors with anti PD-1/PDL1 drugs.
Understanding the role of this chemokine's axis in disease initiation and progression may provide the basis for developing new potential biomarkers as well as therapeutic targets for related pancreatic cancers.
趋化因子是一类参与免疫细胞募集介导过程的小分子分泌肽。趋化因子与多种疾病有关,包括自身免疫性疾病、病毒感染,并且在几种恶性肿瘤的发生和发展中也起着关键作用。CXCL12是一种稳态CXC趋化因子,参与增殖和肿瘤扩散过程。胰腺导管腺癌(PDAC)是最具侵袭性的肿瘤之一,仍然缺乏有效的治疗方法,预后极差。
我们在PubMed和谷歌学术上进行了科学文献检索,包括回顾性、前瞻性研究以及综述,重点关注当前关于CXCL12及其受体CXCR4 - CXCR7在胰腺癌发病机制中新兴作用的研究。
考虑到CXCL12 - CXCR4 - CXCR7轴的免疫调节机制,以及与PDAC微环境的潜在相互作用,已经研究和开发了几种联合治疗方法,以克服PDAC的“冷”免疫状态,如将CXCL12轴抑制剂与抗PD - 1/PDL1药物联合使用。
了解这种趋化因子轴在疾病发生和发展中的作用可能为开发新的潜在生物标志物以及相关胰腺癌的治疗靶点提供依据。