Cancer Genetics, Genomics and Systems Biology Laboratory, Basic and Translational Cancer Research Center (BTCRC), 1516 Nicosia, Cyprus.
Department of Life Sciences, School of Sciences, European University Cyprus, 1516 Nicosia, Cyprus.
Int J Mol Sci. 2024 Mar 23;25(7):3624. doi: 10.3390/ijms25073624.
Intratumoral immune cytolytic activity (CYT), calculated as the geometric mean of granzyme-A (GZMA) and perforin-1 (PRF1) expression, has emerged as a critical factor in cancer immunotherapy, with significant implications for patient prognosis and treatment outcomes. Immune checkpoint pathways, the composition of the tumor microenvironment (TME), antigen presentation, and metabolic pathways regulate CYT. Here, we describe the various methods with which we can assess CYT. The detection and analysis of tumor-infiltrating lymphocytes (TILs) using flow cytometry or immunohistochemistry provide important information about immune cell populations within the TME. Gene expression profiling and spatial analysis techniques, such as multiplex immunofluorescence and imaging mass cytometry allow the study of CYT in the context of the TME. We discuss the significant clinical implications that CYT has, as its increased levels are associated with positive clinical outcomes and a favorable prognosis. Moreover, CYT can be used as a prognostic biomarker and aid in patient stratification. Altering CYT through the different methods targeting it, offers promising paths for improving treatment responses. Overall, understanding and modulating CYT is critical for improving cancer immunotherapy. Research into CYT and the factors that influence it has the potential to transform cancer treatment and improve patient outcomes.
肿瘤内免疫细胞溶细胞活性(CYT),通过计算颗粒酶-A(GZMA)和穿孔素-1(PRF1)表达的几何平均值来评估,已成为癌症免疫治疗的关键因素,对患者预后和治疗结果有重大影响。免疫检查点途径、肿瘤微环境(TME)的组成、抗原呈递和代谢途径调节 CYT。在这里,我们描述了可以评估 CYT 的各种方法。使用流式细胞术或免疫组织化学检测和分析肿瘤浸润淋巴细胞(TILs),可以提供有关 TME 中免疫细胞群体的重要信息。基因表达谱分析和空间分析技术,如多重免疫荧光和成像质谱细胞术,允许在 TME 的背景下研究 CYT。我们讨论了 CYT 具有重要的临床意义,因为其水平升高与积极的临床结果和良好的预后相关。此外,CYT 可用作预后生物标志物并有助于患者分层。通过针对 CYT 的不同方法改变 CYT,可以为改善治疗反应提供有前途的途径。总的来说,了解和调节 CYT 对于改善癌症免疫治疗至关重要。对 CYT 及其影响因素的研究有可能改变癌症治疗并改善患者预后。