Association of cancer progression with elevated expression of programmed cell death protein 1 ligand 1 by upper tract urothelial carcinoma and increased tumor-infiltrating lymphocyte density

Akinori Nukui,Hironori Betsunoh,Takao Kamai,Yoshitatsu Fukabori,Tsunehito Kambara,Hideyuki Abe,Ken-Ichiro Yoshida,Hideo Yuki,Kyoko Arai,Takahiro Narimatsu,Toshiki Kijima,Masahiro Yashi,Minoru Kobayashi

doi:10.1007/s00262-020-02499-7

Abstract

BackgroundIncreased expression of programmed cell death 1 ligand 1 (PD-L1) by tumor cells is thought to be a mechanism through which solid cancers promote immune tolerance. However, the association between PD-L1 expression and the prognosis of upper urinary tract urothelial carcinoma (UTUC) remains unknown.MethodsWe examined immunohistochemical PD-L1 expression and the tumor-infiltrating lymphocyte density (TILD) in 79 patients with UTUC who underwent nephroureterectomy. We classified the tumors into four types based on the combination of PD-L1 expression and TILD, and studied the clinicopathological characteristics of these four tumor types.ResultsElevated expression of PD-L1 by tumor cells and a higher TILD were associated with a worse histological grade, higher pT stage, and higher peripheral blood neutrophil-to-lymphocyte ratio. Elevated expression of PD-L1 by tumor cells, a higher TILD, and type I, III, or IV tumors with elevated expression of either PD-L1 or TILD showed a positive correlation with poorer differentiation and local invasion. These three variables were associated with shorter progression-free survival and overall survival in univariate analysis, but only the latter was an independent determinant according to multivariate analysis. The patients who had type II tumors with lower PD-L1 expression and a lower TILD showed more favorable survival than the other three groups.ConclusionsThese findings suggest that PD-L1 expression and TILs in the tumor microenvironment influence the progression of UTUC. Accordingly, it is important to understand the immunologic characteristics of the tumor microenvironment to develop more effective treatment strategies for this cancer.

Highlights

Upper urinary tract urothelial carcinoma (UTUC) is a relatively uncommon tumor, accounting for < 10% of all urothelial malignancies, its incidence has been increasing [1]
Based on the tumor cell programmed cell death 1 ligand 1 (PD-L1) expression and tumor-infiltrating lymphocyte density (TILD), tumors were classified into four types
Tumor-infiltrating lymphocyte (TIL) PD-L1 expression was not included in this classification [19], we found that within type I tumors (n = 17), nine tumors showed high TILs PD-L1 and eight tumors showed low TILs PD-L1; within type II tumor (n = 34), five tumors showed high TILs PD-L1 and 29 tumors showed low TILs PD-L1

Summary

Introduction

Upper urinary tract urothelial carcinoma (UTUC) is a relatively uncommon tumor, accounting for < 10% of all urothelial malignancies, its incidence has been increasing [1]. Standard first-line chemotherapy for metastatic UC is the combination of gemcitabine and cisplatin (GC) or the combination of methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) [6, 7] Both regimens initially achieve favorable response rates, but neither has much impact on the eventual prognosis [8,9,10]. Elevated expression of PD-L1 by tumor cells, a higher TILD, and type I, III, or IV tumors with elevated expression of either PD-L1 or TILD showed a positive correlation with poorer differentiation and local invasion. These three variables were associated with shorter progression-free survival and overall survival in univariate analysis, but only the latter was an independent determinant according to multivariate analysis. It is important to understand the immunologic characteristics of the tumor microenvironment to develop more effective treatment strategies for this cancer

Methods

Results

Conclusion