Department of Medical Sciences, Uppsala University, 75185, Uppsala, Sweden.
National Bioinformatics Infrastructure Sweden (NBIS), Stockholm University, Stockholm, Sweden.
Sci Rep. 2022 Jul 13;12(1):11960. doi: 10.1038/s41598-022-16077-7.
Understanding the immunological effects of chemotherapy is of great importance, especially now that we have entered an era where ever-increasing pre-clinical and clinical efforts are put into combining chemotherapy and immunotherapy to combat cancer. Single-cell RNA sequencing (scRNA-seq) has proved to be a powerful technique with a broad range of applications, studies evaluating drug effects in co-cultures of tumor and immune cells are however scarce. We treated a co-culture comprised of human colorectal cancer (CRC) cells and peripheral blood mononuclear cells (PBMCs) with the nucleoside analogue trifluridine (FTD) and used scRNA-seq to analyze posttreatment gene expression profiles in thousands of individual cancer and immune cells concurrently. ScRNA-seq recapitulated major mechanisms of action previously described for FTD and provided new insight into possible treatment-induced effects on T-cell mediated antitumor responses.
了解化疗的免疫效应非常重要，特别是现在我们已经进入了一个时代，人们投入越来越多的临床前和临床努力来结合化疗和免疫疗法来治疗癌症。单细胞 RNA 测序（scRNA-seq）已被证明是一种功能强大且应用广泛的技术，但评估药物在肿瘤和免疫细胞共培养物中的作用的研究却很少。我们用核苷类似物氟尿苷（FTD）处理由人结直肠癌（CRC）细胞和外周血单核细胞（PBMC）组成的共培养物，并使用 scRNA-seq 来分析数千个单个癌细胞和免疫细胞的治疗后基因表达谱。scRNA-seq 重现了先前描述的 FTD 的主要作用机制，并为可能的治疗诱导对 T 细胞介导的抗肿瘤反应的影响提供了新的见解。
