Chae Yeon Ji, Kim Jinil, Heo Hwon, Woo Chul-Woong, Kim Sang-Tae, Kim Min Jung, Choi Jong Rip, Kim Dae Hee, Woo Dong-Cheol, Kim Kyung Won, Choi Yoonseok
Department of Convergence Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
Convergence Medicine Research Center, Asan Institute for Life Sciences, Asan Medical Center, Seoul, Republic of Korea.
Transl Oncol. 2019 Sep;12(9):1264-1270. doi: 10.1016/j.tranon.2019.06.006. Epub 2019 Jul 11.
Immune checkpoint inhibitors (ICIs) have become an effective therapeutic option for colorectal cancer and studies on these drugs have therefore increased greatly. Efficacy assessments of ICIs in preclinical orthotopic colorectal cancer using MRI have not been reported however due to the difficulties in conducting colorectal imaging. The purpose of this present study was to investigate the feasibility of using magnetic resonance colonography (MRC) to evaluate the efficacy of an ICI, an anti-PD-L1 antibody, in an orthotopic colorectal cancer mouse model. The mouse model was generated by the engraftment of colorectal cancer cells into the submucosal layer of the colon. Anti-cancer efficacy was assessed by tumor volume and metastatic tumor number analyses, and these values were significantly lower in the PD-L1 antibody-treated group compared to the controls. Histological analyses using H&E and Ki-67 immunohistochemical staining confirmed a highly efficacious tumor growth inhibition and enhanced infiltration by CD4+ and CD8+ lymphocytes in the PD-L1 antibody-treated group. We conclude that MRC has the potential to be used for ICI efficacy assessments against orthotopic colorectal cancer mouse model.
免疫检查点抑制剂(ICIs)已成为结直肠癌的一种有效治疗选择,因此针对这些药物的研究大幅增加。然而,由于进行结直肠成像存在困难,尚未有关于使用磁共振成像(MRI)对临床前原位结直肠癌中ICIs进行疗效评估的报道。本研究的目的是探讨在原位结直肠癌小鼠模型中使用磁共振结肠成像(MRC)评估一种ICI(抗PD-L1抗体)疗效的可行性。通过将结肠癌细胞植入结肠黏膜下层建立小鼠模型。通过肿瘤体积和转移瘤数量分析评估抗癌疗效,与对照组相比,PD-L1抗体治疗组的这些值显著更低。使用苏木精和伊红(H&E)染色以及Ki-67免疫组化染色进行的组织学分析证实,PD-L1抗体治疗组对肿瘤生长有高效抑制作用,且CD4+和CD8+淋巴细胞浸润增强。我们得出结论,MRC有潜力用于评估针对原位结直肠癌小鼠模型的ICI疗效。