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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


Checked for plagiarism Yes

Review by Single-blind

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

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