MUC1‑induced immunosuppression in colon cancer can be reversed by blocking the PD1/PDL1 signaling pathway

Zhang,Yinghui; Dong,Xiangqian; Bai,Liping; Shang,Xueqin; Zeng,Yujian

doi:10.3892/ol.2020.12180

MUC1‑induced immunosuppression in colon cancer can be reversed by blocking the PD1/PDL1 signaling pathway

Authors:
- Yinghui Zhang
- Xiangqian Dong
- Liping Bai
- Xueqin Shang
- Yujian Zeng
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Affiliations: 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, Department of Medical Oncology, The Fourth Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650021, P.R. China, Department of Gastrointestinal Surgery, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650032, P.R. China
Published online on: October 1, 2020 https://doi.org/10.3892/ol.2020.12180
Article Number: 317
Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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.

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