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TLR4 expression correlated with PD-L1 expression indicates a poor prognosis in patients with peripheral T-cell lymphomas

Authors Zhao S, Sun M, Meng H, Ji H, Liu Y, Zhang M, Li H, Li P, Zhang Y, Zhang Q

Received 28 January 2019

Accepted for publication 30 April 2019

Published 23 May 2019 Volume 2019:11 Pages 4743—4756

DOI https://doi.org/10.2147/CMAR.S203156

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Cristina Weinberg

Peer reviewer comments 2

Editor who approved publication: Dr Antonella D'Anneo


Shu Zhao,1,* Mengqi Sun,1,* Hongxue Meng,2 Hongfei Ji,3 Yupeng Liu,4 Minghui Zhang,1 Hongbin Li,1 Pengfei Li,5 Yue Zhang,1 Qingyuan Zhang1

1Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, People’s Republic of China; 2Department of Pathology, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, People’s Republic of China; 3Heilongjiang Cancer Research and Prevention Institute, Harbin, Heilongjiang, People’s Republic of China; 4Department of Epidemiology, School of Public Health, Harbin Medical University, Harbin, Heilongjiang, People’s Republic of China; 5Medical Imaging Center, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, People’s Republic of China

*These authors contributed equally to this work

Background:
Toll-like receptor 4 (TLR4), a member of the pattern recognition receptors, has been reported to be involved in carcinogenesis. However, the clinical impact of TLR4 in peripheral T-cell lymphomas (PTCL) remains unclear.
Methods: The current study, using immunohistochemical staining, first examined TLR4 and programmed cell death-ligand 1 (PD-L1) expression in patients with PTCL, to correlate TLR4 and PD-L1 expression with clinicopathological parameters.
Results: It was found that the rates of high expression of TLR4 and PD-L1 were 41.7% and 45.8%, respectively. TLR4 expression was closely associated with PD-L1 expression. The expression of TLR4 was closely related to primary extranodal site involvement, increased Ann Arbor stage, and low hemoglobin expression, while the expression of PD-L1 was closely related to a low platelet count and multiple extranodal organ involvements (>1). High expression of either TLR4 or PD-L1 indicated a poor survival rate for patients with PTCL. Multivariate analyses further confirmed that increased expression levels of TLR4 and PD-L1 are unfavorable prognostic factors for PTCL.
Conclusion: This study demonstrates that the expressions of TLR4 and PD-L1 are independent predictors of survival time for patients with PTCL. Thus, TLR4 and PD-L1 may serve as potential therapeutic targets in PTCL patients.

Keywords: TLR4, PD-L1, peripheral T-cell lymphomas, non-Hodgkin’s lymphoma, immune checkpoint inhibitor, survival

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