The prognostic value of PD‐L1 expression in upper tract urothelial carcinoma varies according to platelet count

Abstract

Programmed cell death ligand‐1 (PD‐L1) is a ligand for programmed cell death‐1 (PD‐1) that negatively regulates T‐cell activation and plays a crucial role in suppressing anti‐tumor host immunity. Although PD‐L1 is a promising immunotherapy target in various cancers, including urothelial carcinoma (UC), the prognostic significance of PD‐L1 in UC is unclear. As platelets help protect tumor cells from immune elimination in the circulatory system, we hypothesized that tumor PD‐L1 and circulating platelets might synergistically promote tumor metastasis, and that the prognostic significance of PD‐L1 might vary according to platelet count. We immunohistochemically examined tumor PD‐L1 expression in 271 patients with upper tract UC, which revealed PD‐L1 positivity in 31 of 271 cases (11%). The associations of tumor PD‐L1 expression with outcomes varied among patients with high or low platelet counts (P interaction < 0.004). Among patients with high platelet counts (N = 136), PD‐L1 positivity (N = 15) was significantly associated with shorter metastasis‐free survival (univariate hazard ratio [HR]: 6.23, 95% confidence interval [CI]: 2.95‐13.1; multivariate HR: 2.68, 95% CI: 1.27‐5.64) and shorter overall survival (univariate HR: 4.92, 95% CI: 2.14‐11.3, multivariate HR: 2.78, 95% CI: 1.19‐6.51). In contrast, among patients with low platelet counts (N = 135), PD‐L1 positivity (N = 16) was not significantly associated with these outcomes. Our results suggest that tumor PD‐L1 expression and platelet count might interact and help regulate tumor progression. Although a larger prospective study is needed to validate our findings, this relationship is important to consider, as immunotherapies targeting the PD‐1/PD‐L1 axis have gained significant attention as promising therapies for UC.

The Prevalence and Prognostic Role of PD-L1 in Upper Tract Urothelial Carcinoma Patients Underwent Radical Nephroureterectomy: A Systematic Review and Meta-Analysis

“…In the study, PD-L1 was related to UTUC in T stage and tumor grade, and similar findings have been indicated in both UTUC and other types of tumors (23,24,32,33). Results indicated that PD-L1 could not promote the LVI of UTUC, while great heterogeneity existed in the five studies (13,(15)(16)(17)24). However, previous studies have demonstrated that high PD-L1 was related to presence of LVI of tumors (15,34,35).…”

“…We excluded records for the following reasons: article types or not relevant topics (n = 188), studies had few study samples (≤50) or follow-up duration less than 12 months (n = 4), not in English (n = 9), or insufficient survival data (n = 15). Finally, we included eight retrospective cohort studies (1,406 individuals) (13)(14)(15)(16)(17)(23)(24)(25) in the study (shown in Figure 1).…”

“…In recent years, studies have increased dramatically in investigating the association between PD-L1 and survival outcomes in radically resected UTUC patients and the conclusion is still controversial. Some evidence indicated that higher PD-L1 was related to poor survival for UTUC (13,14), while some reported opposing findings (15)(16)(17). Therefore, we formulated clinical questions following the PICOS strategy and firstly assessed whether PD-L1 expression (high or low) was related to survival outcomes or the clinicopathological features in UTUC patients after RNU with no restriction to the study designs through a meta-analysis.…”

The Clinicopathologic and Prognostic Significance of Programmed Cell Death Ligand 1 (PD-L1) Expression in Patients With Prostate Cancer: A Systematic Review and Meta-Analysis

“…The responses strongly correlated with increased PD-1 expression by TILs and increased PD-L1 expression by tumor cells (Pardoll, 2012). Some published studies reported that PD-L1 expression was a negative predictor for prognosis (Zhang et al, 2016; Aghajani et al, 2018; Keller et al, 2018; Miyama et al, 2018), whereas some other studies manifested inconsistent results (Pardoll, 2012; Wang C. et al, 2017; Huang et al, 2018). Various analyses on diverse tumors have showed that the expression of PD-L1 can associate either with poor prognosis, better prognosis or have no connection with prognosis (Ohigashi et al, 2005; Ghebeh et al, 2006; Wu et al, 2006; Hamanishi et al, 2007; Hino et al, 2010; Pardoll, 2012; Iacovelli et al, 2016; Li et al, 2018).…”

The Prognostic Value of PD-1/PD-L1 Expression on Tumor Cells and Tumor-Infiltrating Immune Cells in Patients with Colorectal Cancer: a Systematic Review and Meta-Analysis Protocol

“…The relation between unusual expression of PD-L1 and prognosis or response to the treatment has been observed in several cancers. For example, the relationship between PD-L1 expression and prognosis has been detected in different solid tumors, including urothelial carcinoma, non-small cell lung cancer (NSCLC), and ovarian cancer (9-11). Furthermore, several studies have investigated the relationship between the expression of PD-1/PD-L1 and survival in patients with CRC; some of them have shown that patients with overexpression of these molecules have better survival than others (12, 13), but other studies have illustrated opposite results or no relationship (14, 15).…”