Back to Journals » Cancer Management and Research » Volume 11

High CD3D/CD4 ratio predicts better survival in muscle-invasive bladder cancer

Authors Shi MJ, Meng XY, Wu QJ, Zhou XH

Received 16 October 2018

Accepted for publication 7 February 2019

Published 12 April 2019 Volume 2019:11 Pages 2987—2995

DOI https://doi.org/10.2147/CMAR.S191105

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Cristina Weinberg

Peer reviewer comments 3

Editor who approved publication: Professor Nakshatri


Ming-Jun Shi,1,2 Xiang-Yu Meng,3,4 Qiu-Ji Wu,5 Xiong-Hui Zhou3

1Institut Curie, PSL Research University, CNRS, UMR 144, Paris F-75005, France; 2Department of Urology, Beijing Friendship Hospital, Capital Medical Univeristy , Beijing, 430071, People’s Republic of China; 3Hubei Key Laboratory of Agricultural Bioinformatics, College of Informatics, Huazhong Agricultural University, Wuhan 430070, People’s Republic of China; 4Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, 430071, People’s Republic of China; 5Department of Oncology, Zhongnan Hospital of Wuhan University, Wuhan 430071, People’s Republic of China

Background: Bladder cancer is a common malignancy that affects the human urinary tract. Muscle-invasive bladder cancer (MIBC) is aggressive and has poor prognosis. Previous studies have reported that the tumor-infiltrating lymphocytes (TILs) were associated with MIBC outcome; however, inconsistency remains and mRNA level TIL markers’ prognostic significance in MIBC is unclear. 
Materials and methods: In the present study, we reanalyzed data from four public datasets (the Cancer Genome Atlas for investigation; and CIT, GSE5287, and GSE31684 for validation) to examine the prognostic significance of CD3D, CD4, CD8A, CD3D/CD4 and CD3D/CD8A in MIBC. 
Results: We found that the CD3D/CD4 ratio was a stable independent prognostic factor in MIBC (beta = −0.87, = 0.025); high CD3D/CD4 ratio predicted better survival in MIBC, and the power of this association was much stronger in basal-squamous tumors (beta = −4.73, = 2.67E-06). We also noted that the CD4 expression was significantly higher than CD3D (< 0.05), indicating the presence of CD3−,CD4+, cells which could be immune-suppressing.
Conclusion: The CD3D/CD4 ratio can be viewed as a prognostic marker and a rough measurement for the interaction between immune-effecting CD3+, TILs and immune-suppressing CD3−,CD4+, cells in MIBC, and this interaction may play a particularly important role in anti-cancer immunity in basal-squamous tumors as it has a very strong association with survival in this subtype, and may be used to select potential responders to immunotherapy.

Keywords: bladder cancer, muscle-invasive, tumor-infiltrating lymphocytes, CD3, CD4, CD8, prognosis, immunotherapy, basal-squamous subtype


Creative Commons License This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

Download Article [PDF]