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19.02.2021 | Original Article

Development and validation of a PD-L1/PD-1/CD8 axis-based classifier to predict cancer survival of upper tract urothelial carcinoma after radical nephroureterectomy

Zeitschrift:
Cancer Immunology, Immunotherapy
Autoren:
Junyu Chen, Wenlong Zhong, Meng Yang, Weibin Hou, Xiaofei Wang, Kun Xia, Hao Yu, Meihua Yang, Bingkun Zhou, Bo Wang, Jian Huang, Tianxin Lin
Wichtige Hinweise

Supplementary Information

The online version contains supplementary material available at https://​doi.​org/​10.​1007/​s00262-020-02827-x.
Junyu Chen, Wenlong Zhong and Meng Yang have contributed equally to this work.

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Abstract

The expression status of programmed cell death-ligand 1/programmed cell death 1 (PD-L1/PD-1) and the infiltration of CD8+ T cells in tumor tissues are considered to be related to immunotherapy efficacy and patient prognosis. The purpose of this study is to clarify the prognostic value of the PD-L1/PD-1/CD8 axis, and to develop and validate a comprehensive scoring system based on multiple immune variables to predict cancer survival of upper tract urothelial carcinoma (UTUC) after radical nephroureterectomy (RNU). The immunohistochemical method was used to detect the expression of PD-L1, PD-1, and CD8 in cancer tissues of UTUC patients after RNU. Then, an immunoscore was constructed using the least absolute shrinkage and selection operator (LASSO) Cox regression model in the training cohort (n = 120), and it was verified in the validation cohort (n = 54). We found that infiltration of PD-L1+ immune cells (ICs), stromal PD-1+ tumor-infiltrating lymphocytes (TILs), and intratumoral CD8+ TILs was associated with poor overall survival (OS). The immunoscore based on the three immune variables further divided the patients into low- and high-risk groups, and there was a significant difference in the survival rate. A nomogram was constructed by combining tumor-node-metastasis (TNM) stage and immunoscore, and the area under the curve of the receiver-operating characteristic (ROC) (0.78) for predicting 5-year mortality was better than that of the TNM stage (0.70) and immunoscore (0.76). Our results show that the PD-L1/PD-1/CD8 axis-based classifier have potential clinical application to predict cancer survival of UTUC patients after RNU.

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