Zhang Yinghui, Dong Xiangqian, Bai Liping, Shang Xueqin, Zeng Yujian
Department of Gastroenterology, The Fourth Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650021, P.R. China.
Department of Gastroenterology, The First Affiliated Hospital of Kunming Medical University, Yunnan Institute of Digestive Diseases, Kunming, Yunnan 650032, P.R. China.
Oncol Lett. 2020 Dec;20(6):317. doi: 10.3892/ol.2020.12180. Epub 2020 Oct 1.
Mucin1 (MUC1) upregulation in colon cancer has been linked to poor patient outcomes and advanced stage at diagnosis. This is partially due to MUC1-mediated inhibition of T-cell proliferation affecting efficient lysis by cytotoxic lymphocytes, which contributes to escape from immune surveillance. In the present study, human colorectal cancer tissues were collected, and MUC1-positive and MUC1-negative colon cancer mouse models were prepared; subsequently, the number and function of immune cells in tumor tissues were measured using flow cytometry. The present study revealed that MUC1, as a tumor-associated antigen, can recruit more tumor-infiltrating lymphocytes into the tumor microenvironment compared with MUC1-negative colon cancer, but that these cells could not serve antitumor roles. Conversely, the present study demonstrated that MUC1-positive colon cancer attracted more regulatory T cells (Treg cells), myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs) to the tumor site than MUC1-negative colon cancer. Furthermore, the data suggested that programmed death protein 1 (PD1)-programmed death ligand 1 (PDL1) expression is greater in MUC1-positive colon cancer. Blocking the PD1-PDL1 signaling pathway reduced the percentage of Treg cells, MDSCs and TAMs in the tumor microenvironment, enhanced T-cell cytotoxicity and inhibited tumor growth, prolonging the survival time of MUC1-positive tumor-bearing mice. Therefore, the present study elucidated the role of MUC1 in tumor immune escape and provides a foundation for the application of PDL1 inhibitors to MUC1-positive colon cancer.
黏蛋白1（MUC1）在结肠癌中的上调与患者预后不良和诊断时的晚期阶段有关。部分原因是MUC1介导的T细胞增殖抑制影响了细胞毒性淋巴细胞的有效裂解，这有助于肿瘤逃避免疫监视。在本研究中，收集了人类结直肠癌组织，并制备了MUC1阳性和MUC1阴性结肠癌小鼠模型；随后，使用流式细胞术测量肿瘤组织中免疫细胞的数量和功能。本研究表明，作为肿瘤相关抗原，与MUC1阴性结肠癌相比，MUC1可将更多肿瘤浸润淋巴细胞募集到肿瘤微环境中，但这些细胞不能发挥抗肿瘤作用。相反，本研究证明，与MUC1阴性结肠癌相比，MUC1阳性结肠癌将更多调节性T细胞（Treg细胞）、骨髓来源的抑制细胞（MDSC）和肿瘤相关巨噬细胞（TAM）吸引到肿瘤部位。此外，数据表明，程序性死亡蛋白1（PD1）-程序性死亡配体1（PDL1）在MUC1阳性结肠癌中的表达更高。阻断PD1-PDL1信号通路可降低肿瘤微环境中Treg细胞、MDSC和TAM的百分比，增强T细胞的细胞毒性并抑制肿瘤生长，延长MUC1阳性荷瘤小鼠的生存时间。因此，本研究阐明了MUC1在肿瘤免疫逃逸中的作用，并为将PDL1抑制剂应用于MUC1阳性结肠癌提供了基础。
