Copyright
©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
Overexpression of CD155 is associated with PD-1 and PD-L1 expression on immune cells, rather than tumor cells in the breast cancer microenvironment
Rui-Bin Wang, Yu-Chen Li, Quan Zhou, Shu-Zhen Lv, Ke-Yu Yuan, Jiang-Ping Wu, Yan-Jie Zhao, Qing-Kun Song, Bin Zhu
Rui-Bin Wang, Department of Emergency, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China
Yu-Chen Li, Department of Cancer Research, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China
Quan Zhou, Department of Pathology, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China
Shu-Zhen Lv, Ke-Yu Yuan, Department of Breast Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China
Jiang-Ping Wu, Yan-Jie Zhao, Department of Medical Oncology, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China
Qing-Kun Song, Department of Clinical Epidemiology and Evidence-based Medicine, Beijing Shijitan Hospital, Beijing 100038, China
Bin Zhu, Department of Surgical Oncology, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, China
Author contributions: Wang RB, Li YC and Zhou Q performed the majority of experiments and wrote the manuscript; Lv SZ, Yuan KY, Zhao YJ, and Song QK designed the study and corrected the manuscript; Wu JP and Wang RB contributed to data analysis; Song QK and Zhu B were responsible for designing and performing the study, manuscript reviewing and approval of the final version; Song QK and Zhu B contributed equally to this manuscript; all authors have read and approved the final manuscript.
Supported by Beijing Municipal Committee of Science and Technology, No. Z181100001718090 and Z19110006619041; Beijing Municipal Administration of Hospitals, No. PX2018029; Beijing Shijitan Hospital, Capital Medical University, No. 2017-KF01.
Institutional review board statement: The study was reviewed and approved by the Ethics Committee of Beijing Shijitan Hospital, No. SJEC 2016-111.
Informed consent statement: All study participants or their legal guardian provided informed written consent regarding personal and medical data collection prior to study enrolment.
Conflict-of-interest statement: The authors have no conflict of interest related to the manuscript.
Data sharing statement: The original anonymous dataset is available on request from the corresponding author at
songqingkun@aliyun.com.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
http://creativecommons.org/Licenses/by-nc/4.0/ Corresponding author: Bin Zhu, MD, Professor, Department of Surgical Oncology, Beijing Shijitan Hospital, Capital Medical University, No. 10 Tieyi Road, Haidian District, Beijing 100038, China.
binbinzhu99@sohu.com
Received: July 18, 2020
Peer-review started: July 18, 2020
First decision: August 21, 2020
Revised: August 24, 2020
Accepted: September 25, 2020
Article in press: September 25, 2020
Published online: December 6, 2020
Processing time: 138 Days and 19.2 Hours
BACKGROUND
CD155 is an immune checkpoint protein in cancers and interacts with ligands to regulate the immune microenvironment. The expression of CD155 is correlated with the prognosis and pathological features of breast cancer.
AIM
To investigate the expression status of CD155 and the association with exhausted CD4+ helper and CD8+ cytotoxic tumor infiltrating lymphocytes (TILs) and PD-L1 in the breast cancer microenvironment.
METHODS
One hundred and twenty-six breast cancer patients with invasive ductal breast cancer were consecutively recruited into this study. Immunohistochemistry was used to detect the expression CD155, PD-L1 and PD-1 on tumor-infiltrating immune cells and tumor cells in the microenvironment.
RESULTS
The proportion of patients with CD155 expression was higher in triple negative breast cancer (72.7%) than in Luminal A patients (22.2%, P < 0.05). Patients with positive CD155 expression had a higher percentage of CD4+/PD-1+ helper TILs (30%) than patients with negative CD155 expression (21%, P < 0.05). Patients with positive CD155 expression also had higher cell counts of exhausted CD4+ TILs [47 vs 20/high-power fields (HPF)] and unexhausted CD8+ TILs (30 vs 17/HPF) than patients with negative expression (P < 0.05). CD155 expression was correlated with increased PD-L1 expression in immune cells, 0.8% and 0.02% immune cells expressed PD-L1 in patients with positive and negative CD155 expression, respectively (P < 0.05).
CONCLUSION
CD155 was related to an inhibitory immune breast cancer microenvironment. CD155 was associated with a high proportion of exhausted CD4+ and unexhausted CD8+ TILs and high PD-L1 expression in immune cells.
Core Tip: In this study, we showed that overexpression of CD155 in the breast cancer microenvironment had a significant association with a high level of programmed cell death ligand 1 expression, exhausted CD4+ helper T cells and unexhausted CD8+ cytotoxic T cells. CD155 expression was related to the inhibitory immune microenvironment and may be an immunotherapeutic target in breast cancer.
