Mathias Carolina, Kozak Vanessa Nascimento, Magno Jessica Maria, Baal Suelen Cristina Soares, Dos Santos Victor Henrique Apolonio, Ribeiro Enilze Maria de Souza Fonseca, Gradia Daniela Fiori, Castro Mauro Antonio Alves, Carvalho de Oliveira Jaqueline
Post-Graduation Program in Genetics, Department of Genetics, Federal University of Parana, Curitiba 81530-980, Brazil.
Post-Graduation Program in Bioinformatics, Bioinformatics and Systems Biology Laboratory, Federal University of Paraná, Curitiba 81520-260, Brazil.
Cancers (Basel). 2023 Sep 22;15(19):4682. doi: 10.3390/cancers15194682.
As immune checkpoint inhibitors (ICI) emerge as a paradigm-shifting treatment option for patients with advanced or metastatic cancer, there is a growing demand for biomarkers that can distinguish which patients are likely to benefit. In the case of triple-negative breast cancer (TNBC), characterized by a lack of therapeutic targets, pembrolizumab approval for high-risk early-stage disease occurred regardless of PD-L1 status, which keeps the condition in a biomarker limbus. In this review, we highlight the participation of long non-coding RNAs (lncRNAs) in the regulation of the PD-1/PD-L1 pathway, as well as in the definition of prognostic immune-related signatures in many types of tumors, aiming to shed light on molecules that deserve further investigation for a potential role as biomarkers. We also conducted a bioinformatic analysis to investigate lncRNAs already investigated in PD-1/PDL-1 pathways in other cancer types, considering the TNBC molecular context. In this sense, from the generated data, we evidence here two lncRNAs, UCA1 and HCP5, which have not yet been identified in the context of the tumoral immune response in breast cancer. These candidates can be further explored to verify their use as biomarkers for ICI response. In this article, we present an updated review regarding the use of lncRNA as biomarkers of response to ICI, highlighting the versatility of using these molecules.
随着免疫检查点抑制剂(ICI)成为晚期或转移性癌症患者的一种具有范式转变意义的治疗选择,对能够区分哪些患者可能获益的生物标志物的需求日益增长。在三阴性乳腺癌(TNBC)这种缺乏治疗靶点的情况下,帕博利珠单抗被批准用于高危早期疾病,而不考虑PD-L1状态,这使得该疾病处于生物标志物的边缘地带。在本综述中,我们强调了长链非编码RNA(lncRNA)在PD-1/PD-L1通路调节中的参与,以及在多种肿瘤预后免疫相关特征定义中的作用,旨在揭示值得进一步研究作为生物标志物潜在作用的分子。我们还进行了一项生物信息学分析,考虑到TNBC的分子背景,研究在其他癌症类型中已在PD-1/PDL-1通路中研究过的lncRNA。从这个意义上说,根据生成的数据,我们在此证明了两种lncRNA,即UCA1和HCP5,它们在乳腺癌肿瘤免疫反应背景下尚未被鉴定。这些候选物可以进一步探索,以验证它们作为ICI反应生物标志物的用途。在本文中,我们提供了一篇关于使用lncRNA作为ICI反应生物标志物的最新综述,强调了使用这些分子的多功能性。