Single-cell RNA-seq analysis of immune microenvironment changes in pancreatic cancer following combined EZH2 and KRAS inhibition

Our study demonstrated that combined treatment with the EZH2 inhibitor tazemetostat and the KRAS inhibitor RMC-6236 significantly suppressed the growth of both subcutaneous and orthotopic tumors. To investigate changes in the tumor microenvironment following combined EZH2 and KRAS inhibition in pancreatic cancer, mice bearing subcutaneous KPC tumors were treated with vehicle, RMC-6236 alone, or RMC-6236 in combination with tazemetostat. CD45? cells were isolated and subjected to 10× Genomics single-cell RNA sequencing. Overall design: Mice bearing KPC tumor were treatment with vehicle, RMC-6236 or its combination with tazemetostat for 2 days, and then intratumoral CD45+ cells were isolated using BD FACSAriaIII for sc-RNAseq..

本研究证实，联合应用EZH2抑制剂他泽司他（tazemetostat）与KRAS抑制剂RMC-6236，可显著抑制皮下移植瘤与原位移植瘤的生长。为探究胰腺癌中联合抑制EZH2与KRAS后肿瘤微环境的变化，我们对携带皮下移植KPC瘤的小鼠分别设置溶剂对照组、单药RMC-6236治疗组，以及RMC-6236联合他泽司他的联合治疗组。分离瘤内CD45阳性（CD45+）细胞并开展10×基因组学（10× Genomics）单细胞RNA测序。实验设计：对携带KPC瘤的小鼠分别施以溶剂对照、RMC-6236单药或联合他泽司他治疗2天，随后通过BD FACSAriaIII流式细胞仪分离瘤内CD45阳性细胞，用于单细胞RNA测序（sc-RNAseq）。