# Prognostic value of PD-L1 expression on tumor-infiltrating immune cells and neutrophil-to-lymphocyte ratio in patients with biliary tract cancer

## TL;DR

This study explores how PD-L1 expression on immune cells and the neutrophil-to-lymphocyte ratio (NLR) affect outcomes in biliary tract cancer patients undergoing immunotherapy.

## Contribution

The study identifies PD-L1 on tumor-infiltrating immune cells and NLR as potential prognostic markers for immunotherapy outcomes in biliary tract cancer.

## Key findings

- High PD-L1 expression on tumor-infiltrating immune cells was associated with worse overall survival after immunotherapy.
- Elevated NLR significantly correlated with reduced disease-free and overall survival in biliary tract cancer patients.
- Vascular tumor thrombus, tumor differentiation, and elevated preoperative CA199 levels were significant risk factors for disease-free survival.

## Abstract

The expression of Programmed Death-Ligand 1 (PD-L1) on tumor-infiltrating immune cells (TIICs), plays a crucial role in tumor progression and immune evasion, impacting both the natural immune response and immune-targeted therapeutic strategies. The neutrophil-to-lymphocyte ratio (NLR) has also gained attention as a potential predictive biomarker for immunotherapy efficacy, as it may correlate with treatment outcomes.

To examine the expression of PD-L1 on TIICs and assess the influence of PD-L1 and NLR on immunotherapy outcomes following biliary tract cancers (BTC) recurrence.

From January 1, 2017, to January 1, 2020, this study enrolled 239 patients from the Department of Pancreaticobiliary Surgery at Sun Yat-sen University Cancer Center. Immunohistochemical analysis of PD-L1 on TIICs was conducted on pathological tissue sections from these patients. Clinical data, including overall survival (OS), disease-free survival (DFS), and pathological findings, were collected during follow-up. Statistical analyses were performed to assess outcomes related to the study objectives. Furthermore, data from The Cancer Genome Atlas (TCGA) were utilized to examine PD-L1 expression profiles and related information.

Tumor stage did not differ significantly (P = 0.173), while metastasis stage approached significance (P = 0.093), with a higher proportion of M0 cases in the PD-L1 low group. Univariate analysis revealed vascular tumor thrombus, tumor differentiation, node stage, and preoperative CA199 levels as factors associated with DFS. Notably, vascular tumor thrombus (HR = 1.791, P = 0.002), moderate tumor differentiation (HR = 0.537, P = 0.002), and elevated preoperative CA199 levels (>35, HR = 1.624, P = 0.009) emerged as significant risk factors. Elevated NLR demonstrated a significant association with reduced DFS (HR = 1.54, p = 0.017 one week prior; HR = 1.70, p = 0.007 one month after) and diminished OS (HR = 2.30, p < 0.001 one week prior; HR = 1.94, p = 0.005 one month after). Exploratory analysis in a limited immunotherapy subgroup (n=35) suggested patients exhibiting high PD-L1 levels on TIICs may be associated with worse OS following immunotherapy after recurrence (HR = 3.03, p = 0.036). High NLR, both one month before recurrence (HR = 2.23, p = 0.015) and one month after recurrence (HR = 2.10, p = 0.027), correlated with decreased OS.

PD-L1 expression on TIICs and dynamic NLR may be indicative of prognosis in BTC and could provide insights into immune status and response to immunotherapy after recurrence. These findings highlight the potential value of integrating local immune contexture with systemic inflammatory markers, but further validation in larger and prospective cohorts is warranted.