High Neutrophil-to-Lymphocyte Ratio Predicts a Suppressive Immune Microenvironment and Basal-Like Subtype in Pancreatic Cancer.

BACKGROUND

The neutrophil-to-lymphocyte ratio (NLR) has been utilized as a biomarker predicting prognosis in various cancers. However, it is uncertain whether NLR reflects the immunologic portrait or the molecular subtype of pancreatic cancers.

METHODS

Total 64 pancreatic cancer patients who underwent surgical resection were enrolled and their preoperative serum NLR was calculated. Immunohistochemistry for CD8, CD15, CK5, and GATA6 was performed on tumor tissues to investigate the immunologic microenvironment or molecular subtype of the tumor. ΔNp63 transfection in pancreatic cancer cell lines and subsequent cytokine array were done to investigate the mechanism.

RESULTS

In the clinicopathologic analyses, high-NLR (≥ 3.29) was associated with adenosquamous histology (p = 0.009) and the significantly worse overall (p = 0.003) or disease-free survivals (p = 0.044). In line with the value of serum NLR, tumors in the high-NLR group contained more neutrophils (p = 0.0198) but fewer T lymphocytes (p = 0.0463) than in the low-NLR group. Most of the tumors in the high-NLR group were determined to be the basal-like subtype (p = 0.002). Transfection of ΔNp63, a known key transcription factor driving the basal-like subtype, led to a substantial increase of CCL5, which is a potent chemokine to recruit neutrophils.

CONCLUSIONS

High preoperative NLR is a simple but reliable biomarker predicting a worse prognosis in pancreatic cancer patients, mechanistically because this reflects a suppressive immune microenvironment and also is strongly linked to the aggressive basal-like subtype. Our study provides a rationale to use the NLR for tailored therapy as well as for predicting prognosis.