Peripheral blood neutrophil-to-lymphocyte ratio as a prognostic marker and its association with the tumor-immune microenvironment in pancreatic cancer: a retrospective cohort study

Jing Li; Jiayi Wang; Yuxuan Li; Wenna Jiang; Duo Zuo; Xiuse Zhang; Jiawei Xiao; Kentaro Inamura; Elisa Giovannetti; Li Ren

doi:10.21037/jgo-2025-283

Peripheral blood neutrophil-to-lymphocyte ratio as a prognostic marker and its association with the tumor-immune microenvironment in pancreatic cancer: a retrospective cohort study

J Gastrointest Oncol. 2025 Jun 30;16(3):1248-1257. doi: 10.21037/jgo-2025-283. Epub 2025 Jun 25.

Authors

Jing Li¹, Jiayi Wang¹, Yuxuan Li¹, Wenna Jiang¹, Duo Zuo¹, Xiuse Zhang¹, Jiawei Xiao¹, Kentaro Inamura^{2

3}, Elisa Giovannetti^{4

5}, Li Ren¹

Affiliations

¹ Department of Clinical Laboratory, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.
² Division of Pathology, The Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan.
³ Division of Tumor Pathology, Jichi Medical University, Shimotsuke, Japan.
⁴ Department of Medical Oncology, Amsterdam University Medical Center, VU University, Amsterdam, The Netherlands.
⁵ Cancer Pharmacology Lab, AIRC Start-Up Unit, Fondazione Pisana per la Scienza, San Giuliano Terme, Italy.

Abstract

Background: An elevated peripheral blood neutrophil-to-lymphocyte ratio (NLR) has been reported to be a negative prognostic marker in many types of cancer, including pancreatic ductal adenocarcinoma (PDAC). However, whether NLR is associated with the tumor-immune microenvironment (TIME) in PDAC is unclear. Understanding the interplay between systemic inflammation as reflected by NLR and TIME in PDAC is crucial for identifying prognostic biomarkers and potential therapeutic targets. The aim of this study was to examine the relationship between the NLR and clinical outcomes in patients with early-stage PDAC and the impact of the TIME in PDAC.

Methods: We conducted a retrospective analysis including two cohorts: PDAC patients versus healthy controls and untreated stage I-II PDAC cases. We collected clinical data, including NLR values and followed PDAC patients for overall survival (OS) and relapse-free survival (RFS), and the TIME was evaluated through immunohistochemical staining for CD8⁺ T cells and CD33⁺ myeloid-derived suppressor cells (MDSCs). Statistical analyses were performed to assess the relationship between NLR, clinical outcomes, and TIME components to further determine the value of NLR in reflecting the status of the TIME and predicting outcomes of patients with PDAC.

Results: NLR was negatively associated with OS and RFS in patients with PDAC. Moreover, NLR was found to be a prognostic factor for PDAC and early-stage PDAC. The NLR was inversely correlated with the abundance of tumoral CD8⁺ T cells (r=-0.345, P=0.004) and positively correlated with that of CD33⁺ MDSCs (r=0.407, P=0.001).

Conclusions: Our findings indicate that a high NLR value is closely correlated with poor outcomes in patients with PDAC. In addition, it was significantly associated with the presence of tumoral CD8⁺ tumor-infiltrating lymphocytes and CD33⁺ cells in the TIME of patients with PDAC. NLR may be a biomarker that can inform treat-related decision-making.

Keywords: Pancreatic ductal adenocarcinoma (PDAC); diagnosis; neutrophil-to-lymphocyte ratio (NLR); prediction; tumor-immune microenvironment (TIME).